The discharges of motor axons participating in the tail flick reflex were recorded from nerve filaments innervating the medial longissimus muscles of anesthetized rats. The reflex discharges evoked by stimulation of the tail with either noxious radiant heat or pinch were recorded before and after paralysis of the animals. Nociceptive discharges recorded from motor axons in the paralyzed state showed a strong correlation with those observed in the absence of the paralytic agent. For this reason, the electrophysiological response triggered by noxious input was termed a 'fictive tail flick reflex'. To evaluate the potential applicability of this model in the analysis of pain blocking mechanisms, vaginal stimulation was found to produce a profound reduction to the nociceptive discharges of the fictive tail flick. By eliminating movement artifacts from the experimental paradigm, this model expands our ability to study a basic nociceptive response which was previously limited to behavioral observation.

Recordings were made from 132 raphe- and reticulospinal tract neurons in the medial part of the lower brain stem in 32 anesthetized monkeys. Recording sites were in the nucleus raphe magnus, the rostral nucleus raphe obscurus, and the reticular formation adjacent to the raphe. The neurons were identified by antidromic activation from the upper lumbar spinal cord. Of the population sampled, 83 cells were activated antidromically from the left dorsal lateral funiculus (DLF), 32 from the right DLF, and 17 from both sides. The mean latency for antidromic activation was 8.2 +/- 7.1 ms, corresponding to a mean conduction velocity of 22.8 m/s. No conduction velocities characteristic of unmyelinated axons were observed. Collision tests indicated that raphe-spinal axons that bifurcated to descend in both DLFs branched within the spinal cord. The effects of stimulation in the periaqueductal gray (PAG) or adjacent midbrain reticular formation were tested on 102 spinally projecting neurons in the medial medulla. Of these, 60 cells were excited, 9 cells were inhibited, 8 showed mixed excitation and inhibition, and 25 cells were unaffected. The mean latency for excitation was 11.6 ms and for inhibition, 17.8 ms. Threshold for excitation of raphe- and reticulospinal neurons ranged from 50 to 400 microA. Raphe- and reticulospinal tract cells could often (31/46 cells tested) be excited following stimulation in the ventral posterior lateral nucleus of the thalamus. The mean latency of excitation was 35.6 ms (range, 6-112 ms). Receptive fields could be demonstrated for 80 raphe- and reticulospinal cells, while 48 neurons possessed no demonstrable cutaneous receptive field. Most cells had large excitatory receptive fields, often encompassing the surface of the entire body and face. Some neurons had complex excitatory and inhibitory receptive fields, whereas other cells had large inhibitory receptive fields over much of the surface of the body and face. For most cells (52/55) with excitatory receptive fields, the only effective stimuli were noxious mechanical or noxious heat stimuli. Nonnoxious mechanical stimuli, such as brushing the skin, were capable of activating only a few (3/55) raphe- and reticulospinal neurons, and these were more effectively excited by noxious stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Stimulation in the nucleus raphe magnus produces analgesia in behavioral paradigms and inhibits spinal cord nociceptive neurons. Similar effects result from stimulation of the periaqueductal gray (PAG). Such actions may be mediated via a synaptic link between PAG and nucleus raphe magnus or the adjacent reticular formation. In this study we have examined the effects of biogenic amines applied iontophoretically in the vicinity of nucleus raphe magnus neurons that project to the spinal cord in monkeys. Raphe-spinal tract (RST) neurons were identified by antidromic activation after stimulation of the dorsolateral funiculi at an upper lumbar level. The actions of serotonin, quipazine, norepinephrine, dopamine and acetylcholine (ACh) were tested against the background activity, the activity evoked by glutamate pulses or the excitation of RST cells by stimulation in the PAG. Serotonin, quipazine, norepinephrine and dopamine produced a current-dependent inhibition of background activity and the responses to glutamate pulses in all RST cells tested. No cases of excitation were found. By contrast, ACh enhanced activity produced by glutamate pulses in all RST cells observed. ACh also enhanced the background activity of all but one of the RST cells; however, ACh did not activate cells with little or no background discharge. Serotonin and norepinephrine often inhibited PAG excitation of RST cells. No facilitation of PAG excitation was observed. We conclude that the actions of serotonergic and catecholaminergic agonists on raphe-spinal cells are inhibitory whereas the effect of ACh is facilitatory.

A long-lasting inhibition of the flexion reflex was produced by prolonged electrical stimulation of a peripheral nerve with high intensity and low frequency pulses in decerebrate and spinal cats. The flexion reflex in single active motor axons was recorded from filaments of the L7, Sl or S2 ventral roots. The reflex was elicited either by electrical stimulation of a cutaneous or mixed hind limb nerve or by natural forms of stimulation applied to the foot. A late flexion reflex discharge could be elicited by electrical stimuli that activated Aδ and C afferent fibres. Conditioning stimulation of the common peroneal or tibial nerve at a suprathreshold intensity for C fibers at a rate of 2 Hz for 15 or 30 min produced an inhibition of the flexion reflex late discharges which outlasted the conditioning stimuli. Maximum inhibition on average was to 40.1% and 42.7% of control reflex value in decerebrate and spinal cats, respectively. In decerebrate cats, the duration of inhibition varied from less than 10 min to over 1 h beyond the termination of the conditioning stimuli, depending on the unit (mean = 37.1 ± 13.2 min). However, inhibition lasted over 20 min for all units tested in spinal animals (mean = 38.3 ± 5.4 min). This long-lasting inhibition of the flexion reflex was reversed completely by systemic injection of naloxone hydrochloride (0.05 mg/kg). The long-lasting inhibition of the flexion reflex produced by peripheral nerve stimulation is discussed in relation to peripheral nerve stimulation produced analgesia.