Injections of Algesic Solutions into Muscle Activate the Lateral Reticular Formation: A Nociceptive Relay of the Spinoreticulothalamic Tract.

Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300 µl) of an algesic solution (6% hypertonic saline, pH 4.0 acetate buffer, or 0.05% capsaicin) was made into the gastrocnemius muscle and the distribution of immunolabeled neurons compared to that obtained after control injections of phosphate buffered saline [pH 7.0]. Most labeled neurons in the spinal cord were found in laminae IV-V, VI, VII and X, comparing favorably with other studies, with fewer labeled neurons in laminae I and II. This finding is consistent with the diffuse pain perception due to noxious stimuli to muscles mediated by sensory fibers to deep spinal neurons as compared to more restricted pain localization during noxious stimuli to skin mediated by sensory fibers to superficial laminae. Numerous neurons were immunolabeled in the brainstem, predominantly in the lateral reticular formation (LRF). Labeled neurons were found bilaterally in the caudalmost ventrolateral medulla, where neurons responsive to noxious stimulation of cutaneous and visceral structures lie. Immunolabeled neurons in the LRF continued rostrally and dorsally along the intermediate reticular nucleus in the medulla, including the subnucleus reticularis dorsalis caudally and the parvicellular reticular nucleus more rostrally, and through the pons medial and lateral to the motor trigeminal nucleus, including the subcoerulear network. Immunolabeled neurons, many of them catecholaminergic, were found bilaterally in the nucleus tractus solitarii, the gracile nucleus, the A1 area, the CVLM and RVLM, the superior salivatory nucleus, the nucleus locus coeruleus, the A5 area, and the nucleus raphe magnus in the pons. The external lateral and superior lateral subnuclei of the parabrachial nuclear complex were consistently labeled in experimental data, but they also were labeled in many control cases. The internal lateral subnucleus of the parabrachial complex was labeled moderately. Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently. These data are discussed in terms of an interoceptive, multisynaptic spinoreticulothalamic path, with its large receptive fields and role in the motivational-affective components of pain perceptions.

Modulation of visual inputs to accessory optic system by theophylline during hypoxia.

Neural tissues from fresh water turtles have been electrophysiologically studied in vitro due to their significant resistance to hypoxia. Such neurons have resting membrane potentials that are similar to intact animals and receive similar synaptic inputs evoked by sensory stimuli. One mechanism to reduce the brain's metabolic requirement in the absence of oxygenated blood flow was investigated by blocking adenosine receptors before and during hypoxia. Extracellular and whole-cell patch recordings were made from the basal optic nucleus, whose neurons respond to visual stimuli in vitro. While the addition of the adenosine antagonist theophylline to oxygenated superfusate had minimal effect on the neural activity, theophylline in superfusate bubbled with nitrogen strongly increased activity compared to either oxygenated theophylline or control superfusate bubbled with nitrogen. The increase in spontaneous activity was due to increases to both amplitude and frequency of excitatory synaptic events. Even during these increases, the neurons continued to exhibit their direction-sensitive responses. These results indicate that adenosine may play a role in protecting the viability of the brainstem during hypoxia without reducing visually mediated brainstem reflex control.