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

Panneton WM, Gan Q, Ariel M - PLoS ONE (2015)

Bottom Line: 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.Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, MO, United States of America.

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 (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.

No MeSH data available.


Related in: MedlinePlus

Line drawings illustrating c-Fos activated neurons after a unilateral injection of an algesic solution into the right GCM.Symbols represent a single labeled neuron after injections of buffered normal saline (blue circles), capsaicin (yellow diamonds), low pH acetate buffer (green triangles), and 6% hypertonic saline (red squares). Note the preponderance of immunolabeled neurons in the lateral reticular formation after injections of these algesics into muscle. Also note that immunoreactive neurons in the spinal trigeminal nucleus, parvocellular lateral reticular nucleus and pontine nuclei are not drawn. Numbers to the right of figures represent mm ± 120μm from interaural zero.Abbreviations found on figures:10.1371/journal.pone.0130939.t001A1-noradrenergic cell group of caudal medullaA5-noradrenergic cell group in ventrolateral ponsAmb-nucleus ambiguusAP-area postremacmVLM-caudalmost ventrolateral medullaCu-cuneate nucleusECu-external cuneate nucleusGiA-gigantocellular reticular nucleus, pars alphaGr-gracile nucleusIO-inferior olivary nucleusLC-nucleus locus coeruleusLi-linear nucleus of medullaLRF-lateral reticular formation of brainstemLRt-lateral reticular nucleusMDH-medullary dorsal hornMe5-nucleus of the mesencephalic tract of the trigeminal nerveMo5-motor trigeminal nucleusMRF-medial reticular formationMVe-medial vestibular nucleusPBil-parabrachial nucleus, internal lateral subnucleusPr5-principal trigeminal nucleusPn-pontine nucleiRMg-raphe magnus nucleusRVLM-pressor area of the rostral medullaSol, NTS-nucleus tractus solitariiSO-superior olivary nucleusSp5I-nucleus of the spinal tract of the trigeminal nerve, interpolar partSp5O-nucleus of the spinal tract of the trigeminal nerve, oral partSRD-subnucleus reticularis dorsalisSVe-spinal vestibular nucleusTz-trapezoid nucleusVC-ventral cochlear nucleusVLL-ventral nucleus of lateral leminiscusVMM-ventromedial medullabc-brachium conjunctivumg7-genu of facial nervemcp-middle cerebellar pedunclem5-motor root of 5nn7-facial nervepy-pyramidal tractsol-tractus solitariisp5-spinal tract of the trigeminal nerve7-facial motor nucleus7n-facial nerve root12-hypoglossal motor nucleus
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pone.0130939.g001: Line drawings illustrating c-Fos activated neurons after a unilateral injection of an algesic solution into the right GCM.Symbols represent a single labeled neuron after injections of buffered normal saline (blue circles), capsaicin (yellow diamonds), low pH acetate buffer (green triangles), and 6% hypertonic saline (red squares). Note the preponderance of immunolabeled neurons in the lateral reticular formation after injections of these algesics into muscle. Also note that immunoreactive neurons in the spinal trigeminal nucleus, parvocellular lateral reticular nucleus and pontine nuclei are not drawn. Numbers to the right of figures represent mm ± 120μm from interaural zero.Abbreviations found on figures:10.1371/journal.pone.0130939.t001A1-noradrenergic cell group of caudal medullaA5-noradrenergic cell group in ventrolateral ponsAmb-nucleus ambiguusAP-area postremacmVLM-caudalmost ventrolateral medullaCu-cuneate nucleusECu-external cuneate nucleusGiA-gigantocellular reticular nucleus, pars alphaGr-gracile nucleusIO-inferior olivary nucleusLC-nucleus locus coeruleusLi-linear nucleus of medullaLRF-lateral reticular formation of brainstemLRt-lateral reticular nucleusMDH-medullary dorsal hornMe5-nucleus of the mesencephalic tract of the trigeminal nerveMo5-motor trigeminal nucleusMRF-medial reticular formationMVe-medial vestibular nucleusPBil-parabrachial nucleus, internal lateral subnucleusPr5-principal trigeminal nucleusPn-pontine nucleiRMg-raphe magnus nucleusRVLM-pressor area of the rostral medullaSol, NTS-nucleus tractus solitariiSO-superior olivary nucleusSp5I-nucleus of the spinal tract of the trigeminal nerve, interpolar partSp5O-nucleus of the spinal tract of the trigeminal nerve, oral partSRD-subnucleus reticularis dorsalisSVe-spinal vestibular nucleusTz-trapezoid nucleusVC-ventral cochlear nucleusVLL-ventral nucleus of lateral leminiscusVMM-ventromedial medullabc-brachium conjunctivumg7-genu of facial nervemcp-middle cerebellar pedunclem5-motor root of 5nn7-facial nervepy-pyramidal tractsol-tractus solitariisp5-spinal tract of the trigeminal nerve7-facial motor nucleus7n-facial nerve root12-hypoglossal motor nucleus

Mentions: Sections from all experiments were examined with a Nikon E800 microscope equipped with brightfield and fluorescent optics, photographed digitally (Olympus 41BX microscope with DP-72 digital camera; Research Microscopy Core, Saint Louis University), and processed and saved on a computer. Composite pictures of whole sections were stitched using functions in Microsoft ICE (Microsoft Image Composite Editor; http://research.microsoft.com/en-us/um/redmond/groups/ivm/ice/). The reader may magnify these photomontages to see all of the data from these sections. The location of neurons labeled with c-Fos was reconstructed for Fig 1 using a Neurolucida System (MicroBrightField, Cochester, VT) interfaced with a Nikon E600 microscope. Four experiments were selected with strong labeling contrast: a control case and three with an injection of each algesic into the gastrocnemius muscle. Labeled neurons from those brains were superimposed onto standard brain sections available to our laboratory. Photomicrographs were adjusted in Adobe Photoshop CS2 software using levels, brightness and contrast, and figures were labeled in Adobe Illustrator CS2 software (Adobe Systems, San Jose, CA).


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

Panneton WM, Gan Q, Ariel M - PLoS ONE (2015)

Line drawings illustrating c-Fos activated neurons after a unilateral injection of an algesic solution into the right GCM.Symbols represent a single labeled neuron after injections of buffered normal saline (blue circles), capsaicin (yellow diamonds), low pH acetate buffer (green triangles), and 6% hypertonic saline (red squares). Note the preponderance of immunolabeled neurons in the lateral reticular formation after injections of these algesics into muscle. Also note that immunoreactive neurons in the spinal trigeminal nucleus, parvocellular lateral reticular nucleus and pontine nuclei are not drawn. Numbers to the right of figures represent mm ± 120μm from interaural zero.Abbreviations found on figures:10.1371/journal.pone.0130939.t001A1-noradrenergic cell group of caudal medullaA5-noradrenergic cell group in ventrolateral ponsAmb-nucleus ambiguusAP-area postremacmVLM-caudalmost ventrolateral medullaCu-cuneate nucleusECu-external cuneate nucleusGiA-gigantocellular reticular nucleus, pars alphaGr-gracile nucleusIO-inferior olivary nucleusLC-nucleus locus coeruleusLi-linear nucleus of medullaLRF-lateral reticular formation of brainstemLRt-lateral reticular nucleusMDH-medullary dorsal hornMe5-nucleus of the mesencephalic tract of the trigeminal nerveMo5-motor trigeminal nucleusMRF-medial reticular formationMVe-medial vestibular nucleusPBil-parabrachial nucleus, internal lateral subnucleusPr5-principal trigeminal nucleusPn-pontine nucleiRMg-raphe magnus nucleusRVLM-pressor area of the rostral medullaSol, NTS-nucleus tractus solitariiSO-superior olivary nucleusSp5I-nucleus of the spinal tract of the trigeminal nerve, interpolar partSp5O-nucleus of the spinal tract of the trigeminal nerve, oral partSRD-subnucleus reticularis dorsalisSVe-spinal vestibular nucleusTz-trapezoid nucleusVC-ventral cochlear nucleusVLL-ventral nucleus of lateral leminiscusVMM-ventromedial medullabc-brachium conjunctivumg7-genu of facial nervemcp-middle cerebellar pedunclem5-motor root of 5nn7-facial nervepy-pyramidal tractsol-tractus solitariisp5-spinal tract of the trigeminal nerve7-facial motor nucleus7n-facial nerve root12-hypoglossal motor nucleus
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4496070&req=5

pone.0130939.g001: Line drawings illustrating c-Fos activated neurons after a unilateral injection of an algesic solution into the right GCM.Symbols represent a single labeled neuron after injections of buffered normal saline (blue circles), capsaicin (yellow diamonds), low pH acetate buffer (green triangles), and 6% hypertonic saline (red squares). Note the preponderance of immunolabeled neurons in the lateral reticular formation after injections of these algesics into muscle. Also note that immunoreactive neurons in the spinal trigeminal nucleus, parvocellular lateral reticular nucleus and pontine nuclei are not drawn. Numbers to the right of figures represent mm ± 120μm from interaural zero.Abbreviations found on figures:10.1371/journal.pone.0130939.t001A1-noradrenergic cell group of caudal medullaA5-noradrenergic cell group in ventrolateral ponsAmb-nucleus ambiguusAP-area postremacmVLM-caudalmost ventrolateral medullaCu-cuneate nucleusECu-external cuneate nucleusGiA-gigantocellular reticular nucleus, pars alphaGr-gracile nucleusIO-inferior olivary nucleusLC-nucleus locus coeruleusLi-linear nucleus of medullaLRF-lateral reticular formation of brainstemLRt-lateral reticular nucleusMDH-medullary dorsal hornMe5-nucleus of the mesencephalic tract of the trigeminal nerveMo5-motor trigeminal nucleusMRF-medial reticular formationMVe-medial vestibular nucleusPBil-parabrachial nucleus, internal lateral subnucleusPr5-principal trigeminal nucleusPn-pontine nucleiRMg-raphe magnus nucleusRVLM-pressor area of the rostral medullaSol, NTS-nucleus tractus solitariiSO-superior olivary nucleusSp5I-nucleus of the spinal tract of the trigeminal nerve, interpolar partSp5O-nucleus of the spinal tract of the trigeminal nerve, oral partSRD-subnucleus reticularis dorsalisSVe-spinal vestibular nucleusTz-trapezoid nucleusVC-ventral cochlear nucleusVLL-ventral nucleus of lateral leminiscusVMM-ventromedial medullabc-brachium conjunctivumg7-genu of facial nervemcp-middle cerebellar pedunclem5-motor root of 5nn7-facial nervepy-pyramidal tractsol-tractus solitariisp5-spinal tract of the trigeminal nerve7-facial motor nucleus7n-facial nerve root12-hypoglossal motor nucleus
Mentions: Sections from all experiments were examined with a Nikon E800 microscope equipped with brightfield and fluorescent optics, photographed digitally (Olympus 41BX microscope with DP-72 digital camera; Research Microscopy Core, Saint Louis University), and processed and saved on a computer. Composite pictures of whole sections were stitched using functions in Microsoft ICE (Microsoft Image Composite Editor; http://research.microsoft.com/en-us/um/redmond/groups/ivm/ice/). The reader may magnify these photomontages to see all of the data from these sections. The location of neurons labeled with c-Fos was reconstructed for Fig 1 using a Neurolucida System (MicroBrightField, Cochester, VT) interfaced with a Nikon E600 microscope. Four experiments were selected with strong labeling contrast: a control case and three with an injection of each algesic into the gastrocnemius muscle. Labeled neurons from those brains were superimposed onto standard brain sections available to our laboratory. Photomicrographs were adjusted in Adobe Photoshop CS2 software using levels, brightness and contrast, and figures were labeled in Adobe Illustrator CS2 software (Adobe Systems, San Jose, CA).

Bottom Line: 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.Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, MO, United States of America.

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 (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.

No MeSH data available.


Related in: MedlinePlus