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

Abstract

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 (300μl) 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.

Reticular Formation and Pain: The Past and the Future

“…Incidentally, it must be noted that the magnitude of activation of VLMlat neurons, as measured by the expression of the c- fos protooncogene, is directly correlated with the magnitude of activation of lamina I neurons (Pinto et al, 2006 ), which reinforces the functional relevance of the above mentioned lamina I-VLMlat-lamina I loop. Recent studies showed that VLMlat neurons respond to diffuse noxious stimulation of the muscles (Panneton et al, 2015 ) and a new role for the VLMlat as a component of the classical spinoreticulothalamic pathway has emerged in which this RF region is proposed to have a key relay role. The poor activation of more medial components of the VLM, namely the LRt, in response to noxious stimulation along with the role of the LRt in motor control suggests that the VLM may be specially positioned to provide an integrated response to an acute stimulus, namely to the classical “fight or flight” response.…”

The Effect of Pre-Electroacupuncture on Nociceptive Discharges of Spinal Wide Dynamic Range Neurons in Rat

“…[32][33][34] Application of HS at gastrocnemius muscle induced mechanical hyperalgesia 35,36 and c-Fos expression in deep (IV-VI) lamina of SDH of L4-6 segments. 37,38 In this study, WDR neurons in deep lamina IV-VI of SDH exhibited obvious discharges, indicating that WDR neurons were activated following intramuscular injection of HS. Interestingly, pretreatment of EA effectively inhibits nociceptive activities of WDR neurons and the effects were dependent on intensities and locations of intervention, showing the preventive analgesic effects of pre-EA.…”

Photic Sneeze Reflex: Another Variant of the Trigeminocardiac Reflex?

“…This hypothesis might explain why the TCR and its subgroups are better documented during surgery [76][77][78]. But it also opens the window to further (potential) risk factors [79][80][81], a better understanding of neuroanatomy [82,83] and might explain the influence of positive psychology on the course of different neurological diseases [84][85][86]. In such a context, the TCR also helps to understand the physiology of the nervous system better and to develop new models of it [87][88][89][90][91][92].…”