Spastic Long-Lasting Reflexes in the Awake Rat After Sacral Spinal Cord Injury

Abstract

Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury. J Neurophysiol 91: 2247-2258, 2004; 10.1152/jn.00946.2003. Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with Ͼ6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (Յ52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 ϫ T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300 -500 ms long reflex, similar to the onset of the longlasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by descending control. This pEPSP is released from inhibition immediately after injury but does not produce a long-lasting reflex because of a lack of motoneuron excitability. With chronic injury the motoneuron excitability is increased markedly, and the pEPSP then triggers sustained motoneuron discharges associated with long-lasting reflexes and muscle spasms.

Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

“…Shortly after the injury, the excitability of the spinal cord decreases because this excitatory influence of the brainstem on motoneurons is lost. However, motoneurons slowly recover the capacity to generate PICs, which are, in large part, responsible for longlasting reflexes and spasms (49,50). Both 5-HT 2B Rs and 5-HT 2C Rs, but not 5-HT 2A Rs, are involved in this up-regulation of PICs (44).…”

Hip-phase-dependent flexion reflex modulation and expression of spasms in patients with spinal cord injury

“…3) due to hip movement and/or to the stimulus (Nickolls et al, 2004). Nonetheless, spasms have also been attributed to slowly activating voltagedependent persistent inward currents that enable motoneurons to produce prolonged discharges in response to brief inputs Bennett et al, 2004), which in turn are under control of descending monoaminergic systems that are impaired in people with a SCI.…”

Spastic Tail Muscles Recover From Myofiber Atrophy and Myosin Heavy Chain Transformations in Chronic Spinal Rats

“…However, in humans and in some animal models, considerable neuromuscular activity sometimes develops after SCI in the form of spasticity, a syndrome that includes hyperreflexia, hypertonus, and long-lasting spasms (Bennett et al 2004;Fujimori et al 1968;Heckman 1994;Kuhn and Macht 1948;Lance and Burke 1974;Ritz et al 1992;Taylor et al 1997). Furthermore, preservation of slow (Hidler et al 2002;Thomas and Ross 1997;Zijdewind and Thomas 2003) and fatigue-resistant (Hartkopp et al 2003) muscle contractile properties has been observed in conjunction with spasticity after SCI in humans.…”

“…Recently, it has been shown that after sacral spinal cord transection, rats develop a pronounced spastic syndrome in the segmental muscles of the tail over a period of months (chronic spinal rats) (Bennett et al 1999(Bennett et al , 2001(Bennett et al , 2004. This spasticity is associated with large muscle spasms lasting many seconds that are evoked by brief, normally innocuous sensory inputs to the tail, such as brushing of the tail on the cage bedding during walking; further, there is ongoing spontaneous EMG activity in the muscles lasting for hours at a time (Bennett et al 2001).…”

“…In sacral spinal rats, the tail muscles are flaccid for the first 2 wk; then spasticity slowly develops, and the muscles become completely spastic 2-3 mo postinjury (Bennett et al 2004). In response to reduced muscle activity after spinal cord transection in other preparations without spasticity, transformations in rat myofiber types generally occur as early as 1 wk after SCI (Dupont-Versteegden et al 1998) but require months to reach a new steady state .…”