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.

Highlights

  • Chronic muscle and joint pain afflicts many, especially the aged [1]

  • Unlike the effect of skin stimulation, we show that few neurons were activated with c-Fos in the superficial dorsal horn of the spinal cord and that most of those activated neurons were in laminae IV-V, VI-VII and X

  • After a gastrocnemius muscle (GCM) was injected with normal saline, there were few immunolabeled neurons with c-Fos antibodies in the spinal cord but some were labeled in the brainstem (Fig 1, blue circles)

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Summary

Introduction

Chronic muscle and joint pain afflicts many, especially the aged [1]. The aging population is more prone to take prescribed statin drugs, often resulting in muscle pain [3] that is dull and poorly localized. The smallest fibers innervating muscle (fiber groups III and IV) are thought to relay nociceptive signals [4, 5]. 58% of fibers innervating the sternocleidomastoid muscle are unmyelinated, and 60% of these may be sensory fibers [6]. C and Aδ fibers end in muscle as free nerve endings [4, 7, 8]; similar small fibers innervate joints [9], 80% of which are c-fibers

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