Parametric and pharmacological studies of midbrain suppression of the hind limb flexion withdrawal reflex in the rat.
These experiments quantitatively analyzed effects of electrical midbrain stimulation on a nociceptive hind limb flexion reflex in rats anesthetized with sodium pentobarbital. We recorded the force of isometric hind limb flexion withdrawal, and related flexor electromyographic (EMG) activity, elicited by noxious heat (42-54 degrees C, 10 sec) applied to the ventral hind paw. Several hind limb flexors including biceps femoris were active during the reflex. Quantified reflex responses to identical noxious heat stimuli delivered every 2 min were constant in magnitude and were reduced or abolished during stimulation (100 msec trains at 100 Hz, 3/sec, 15-325 microA) in the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF). LRF was significantly more effective than PAG stimulation in suppressing reflex responses. The magnitude of the reflex responses increased with graded increases in the temperature of the noxious heat stimulus. The slope of the temperature-response relationship was significantly reduced during PAG stimulation, whereas it was shifted toward higher temperatures with significantly increased threshold during LRF stimulation. To investigate possible transmitters involved, we tested if PAG- or LRF-evoked reflex suppression was affected following systemic administration of the opiate antagonist naloxone, the serotonin antagonist methysergide, the noradrenergic antagonist phentolamine, or the cholinergic antagonist scopolamine. Naloxone had little effect, while methysergide and phentolamine reduced PAG- and LRF-evoked reflex suppression in about one-half of the cases. Scopolamine largely reduced PAG- and LRF-evoked reflex suppression (in 8/9 and 4/6 rats, respectively). These results indicate that the flexion reflex is under parametrically but not pharmacologically distinct inhibitory midbrain controls.