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Changes in the excitability of the hamstring flexor withdrawal reflex produced by conditioning stimuli applied to C-afferent fibers of different origins have been examined in the decerebrate spinal rat. In the absence of conditioning stimuli, the flexor reflex elicited by a standard suprathreshold mechanical stimulus to the toes is stable when tested repeatedly for hours. Three categories of conditioning stimuli have been used in an attempt to modify the excitability of the flexor reflex; electrical stimulation of a cutaneous (sural) nerve or a muscle (gastrocnemiussoleus) nerve at C-fiber strength, the application of mustard oil, a chemical irritant that activates chemosensitive C-afferents, to the skin or injected intramuscularly and intraarticularly; and the indirect activation of high-threshold muscle afferents by fused tetanic contractions of the tibia1 muscles. Conditioning stimuli of an intensity sufficient to activate C-afferent fibers result in a heterosynaptic facilitation of the flexor motoneuronal response to the standard test input, which lasts from 3 min to more than 3 hr, depending on the stimulus and the C-afferents activated. Pretreatment of the sciatic nerve with the C-fiber neurotoxin capsaicin abolishes all the postconditioning facilitations, which is an indication that it is likely that it is C-afferents that are primarily responsible for the facilitatory effects of the conditioning stimuli, although some A delta afferents may contribute. Capsaicin pretreatment does not modify the reflex response to the test stimulus. The most prolonged increase in the excitability of the flexor reflex resulted from intraarticular injections of 5 11 mustard oil. Using the subsequent injection of lignocaine intraarticulary, it was found that the prolonged facilitation of the reflex is triggered by the afferent input generated by the conditioning stimulus and does not require an ongoing input for its maintenance. These results indicate that there is a spectrum of central changes in the stimulus response relations of the spinal cord resulting from the activation of C-fibers of different origins. The prolonged duration of some of these changes means that the peripheral activation of C-afferents will modify the functional response of the spinal cord to other inputs applied long after the conditioning input, and this may be responsible for some of the sensory and motor alterations found after peripheral tissue injury.Unmyelinated C-fibers constitute the majority of afferents in the dorsal roots of all mammalian species (Willis and Coggeshall, 1978). In the rat, only cutaneous C-fibers have been studied, and most of these are activated exclusively by intense me-

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