Electrophysiological characterization of the projection from the nucleus raphe magnus to the lateral reticular nucleus: possible role of an excitatory amino acid in synaptic activation.

Numerous studies have shown that the lateral reticular nucleus (LRN), located in the caudal ventrolateral medulla, is an important nuclear region in the descending analgesia system. Activation of this brainstem region, either electrically or chemically, results in a reduction in nociceptive threshold. In addition, destruction of LRN abolishes the tonic descending inhibition present on dorsal horn neurons. Recent neuroanatomical tracing studies have shown that the nucleus raphe magnus (NRM), long implicated in nociception, sends direct projections to LRN; however, no information exists regarding the physiological characteristics of this pathway, nor its role in the endogenous descending analgesia system. The purpose of this study was to physiologically characterize the synaptic influence(s) of projections from the NRM to the LRN using electrophysiological recording, electrical and chemical stimulation, and iontophoretic techniques. Sixty-one percent of LRN neurons responded to single pulse stimulation of NRM; 52% of the responsive cells were excited and 48% were inhibited. The mean latency to onset of excitation was 4.9 +/- 1.2 ms. High frequency (100 Hz) electrical stimulation of NRM influenced 69/102 neurons; 52% (36/69) were excited, while 48% (33/69) were inhibited. Microinjection of glutamate into NRM significantly modified the discharge of 83% (93/112) of LRN cells tested; of these, 71% were inhibited, while 29% were excited. In 35 cells the effects of the excitatory amino acid antagonist kynurenic acid (KYN) were studied. In 75% of the cells excited by glutamate administration into the NRM (18/24), KYN partially antagonized this response. In 11 LRN cells inhibited by NRM chemical stimulation, KYN had no effect on this inhibition. Overall, 95% of the LRN cells responsive to NRM stimulation were also responsive to noxious peripheral stimulation, indicating that these cells are receiving ascending information from the spinal cord regarding somatosensory stimulation as well as receiving descending input from the NRM. It is concluded that LRN neurons are highly responsive to both noxious peripheral stimulation and NRM efferent activation, and that this region plays a significant role as an integrator for both ascending and descending information.