Temporal Summation of C-Fiber Afferent Inputs: Competition Between Facilitatory and Inhibitory Effects on C-Fiber Reflex in the Rat

Abstract

Long-lasting facilitations of spinal nociceptive reflexes resulting from temporal summation of nociceptive inputs have been described on many occasions in spinal, nonanesthetized rats. Because noxious inputs also trigger powerful descending inhibitory controls, we investigated this phenomenon in intact, halothane-anesthetized rats and compared our results with those obtained in other preparations. The effects of temporal summation of nociceptive inputs were found to be very much dependent on the type of preparation. Electromyographic responses elicited by single square-wave electrical shocks (2 ms, 0.16 Hz) applied within the territory of the sural nerve were recorded in the rat from the ipsilateral biceps femoris. The excitability of the C-fiber reflex recorded at 1.5 times the threshold (T) was tested after 20 s of electrical conditioning stimuli (2 ms, 1 Hz) within the sural nerve territory. During the conditioning procedure, the C-fiber reflex was facilitated (wind-up) in a stimulus-dependent fashion in intact, anesthetized animals during the application of the first seven conditioning stimuli; thereafter, the magnitude of the responses reached a plateau and then decreased. Such a wind-up phenomenon was seen only when the frequency of stimulation was 0.5 Hz or higher. In spinal, unanesthetized rats, the wind-up phenomenon occurred as a monotonic accelerating function that was obvious during the whole conditioning period. An intermediate picture was observed in the nonanesthetized rat whose brain was transected at the level of the obex, but the effects of conditioning were profoundly attenuated when such a preparation was anesthetized. In intact, anesthetized animals the reflex was inhibited in a stimulus-dependent manner during the postconditioning period. These effects were not dependent on the frequency of the conditioning stimulus. Such inhibitions were blocked completely by transection at the level of the obex, and in nonanesthetized rats were then replaced by a facilitation. A similar long-lasting facilitation was seen in nonanesthetized, spinal rats. It is concluded that, in intact rats, an inhibitory mechanism counteracts the long-lasting increase of excitability of the flexor reflex seen in spinal animals after high-intensity, repetitive stimulation of C-fibers. It is suggested that supraspinally mediated inhibitions also participate in long term changes in spinal cord excitability after noxious stimulation.

Windup in Dorsal Horn Neurons Is Modulated by Endogenous Spinal μ-Opioid Mechanisms

“…This is consistent with previous findings that induction of windup in rodents requires C-fiber activation at frequen- cies Ͼ0.3 Hz under normal conditions (Gozariu et al, 1997;Herrero et al, 2000). An important observation is that the average C-component for the last 10 stimuli during 0.2 Hz stimulation was significantly higher in MOR Ϫ/Ϫ mice than that in wildtype mice, suggesting an enhanced windup (Fig.…”

Enhanced Wind-Up of the C-Fiber-Mediated Nociceptive Flexor Reflex Movement Following Painful Diabetic Neuropathy in Mice

“…In non-spinalized animals, wind-up is strongly modulated by supraspinal descending influences. The descending inhibitory mechanism counteracts the progressive increase in the withdrawal reflex, leading to the habituation of wind-up (15).…”

“…Apart from the long-lasting descending inhibitory control that continues even after cessation of the CS in non-spinalized, halothane-anesthetized rats (15), the inhibitory control after the CS is likely to be less effective in non-spinalized, urethane-anesthetized mice, which was evidenced by the existence of post-CS facilitation in our study and others (16,17). Our finding that post-CS facilitation of the Ad -fiber-mediated withdrawal reflex after the CS was reduced in diabetic mice (Fig.…”

Discharge of Raphe Magnus on and offCells Is Predictive of the Motor Facilitation Evoked by Repeated Laser Stimulation

“…Similarly, in humans, the second of two brief heat stimuli applied at interstimulus intervals of 3-7 sec elicits more pain than does the first (Vierck et al, 1997). When electrical shock is used, double stimulation does not consistently evoke facilitation (Arendt-Nielsen et al, 1994Gozariu et al, 1997). For instance, repeated electrical stimulation of the sural nerve, at intensities sufficient to activate C fibers, facilitates the late motor reflex at interstimulus intervals of 1-2 sec in rats (Gozariu et al, 1997) but not humans (Arendt-Nielsen et al, 2000).…”

“…When electrical shock is used, double stimulation does not consistently evoke facilitation (Arendt-Nielsen et al, 1994Gozariu et al, 1997). For instance, repeated electrical stimulation of the sural nerve, at intensities sufficient to activate C fibers, facilitates the late motor reflex at interstimulus intervals of 1-2 sec in rats (Gozariu et al, 1997) but not humans (Arendt-Nielsen et al, 2000). Electrical stimulation differs from thermal stimulation in that it activates all afferent types and is completely synchronous.…”