Considerations concerning the neurobiological basis of muscle pain

1991 ◽  
Vol 69 (5) ◽  
pp. 610-616 ◽  
Author(s):  
S. Mense
Keyword(s):  
Dorsal Horn ◽  
Muscle Pain ◽  
Receptive Fields ◽  
Spinal Reflexes ◽  
Noxious Stimulation ◽  
Dorsal Horn Neurone ◽  
Additional Input ◽  
Degree Of Convergence ◽  
Chronic Muscle Pain ◽  
Stimulation Of

Nociceptors in skeletal muscle can be sensitized by substances that are released from pathologically altered tissue. In the sensitized state, nociceptors can be activated by low-intensity stimulation; this is probably one of the mechanisms producing deep tenderness. Dorsal horn cells processing input from muscle nociceptors often have multiple receptive fields and additional input from other deep tissues or skin. This may be one of the reasons for the diffuse and ill-localized nature of muscle pain. The degree of convergence from deep tissues and skin in neurones with muscle input can be increased by noxious stimulation of deep tissues. This mechanism might explain phenomena such as spread and referral of muscle pain. In the development of chronic muscle pain, vicious circles may be involved which operate locally in the damaged tissue or via spinal reflexes that alter the biochemical environment of the nociceptors in skeletal muscle.Key words: nociceptor, dorsal horn neurone, sensitization, muscle pain, pain referral.

Neuronal and behavioural responses in rats during noxious stimulation of the tail

1977 ◽  
Vol 197 (1127) ◽  
pp. 169-194 ◽  
Keyword(s):  
Dorsal Horn ◽  
Receptive Fields ◽  
Temperature Response ◽  
Threshold Temperature ◽  
Noxious Stimulation ◽  
Mechanical Stimuli ◽  
Response Curves ◽  
Ventrobasal Nucleus ◽  
Behavioural Experiments ◽  
Stimulation Of

In rats anaesthetized with urethane, extracellular unit activity has been recorded from neurones in the central nervous system during noxious stimulation of the tail. Accurately graded and sustained stimulation was achieved by immersing the whole tail in water at controlled temperatures. Neurones were found chiefly in the marginal layers of the dorsal horn near the entry of the dorsal roots supplying the tail and in the ventrobasal nucleus of the thalamus; a few neurones were also found in the somatosensory cortex. Both dorsal horn units and thalamic units showed very similar responses as the tail temperature was gradually raised. At 42°C there was an increase in firing rate which rose sharply with increasing temperatures to reach a maximum at 46°C. At higher temperatures activ­ity declined and at temperatures above 50°C was largely extinguished. The temperature-response curves were bell-shaped. The decline in activity depended on temperature and not on time: sustained firing for many minutes was seen when temperature was at or just below the peak of the bell-shaped curve. The dorsal horn and thalamic cells also responded to noxious mechanical stimulation of the tail. The receptive fields at both levels were similar, being variable in size, often bilateral and sometimes covering the whole tail. None of the central neurones showed any response to noxious stimulation other than on the tail; neither did they respond to movement of the tail nor to light mechanical stimuli applied to the tail or elsewhere. In behavioural experiments conscious rats had their tails exposed to water at various temperatures. The rats lifted their tails from the water at a threshold temperature of 43.7 ± 0.6°C, i. e. just above the threshold for the central nociceptive neurones. The findings are compatible with a specific nociceptive pathway ascending to the ventrobasal thalamus.

Responses of spinal trigeminal neurons to noxious stimulation of paranasal cavities – a rat model of rhinosinusitis headache

Cephalalgia ◽  
2020 ◽  
pp. 033310242097046
Author(s):  
Michael Koch ◽  
Julika Sertel-Nakajima ◽  
Karl Messlinger
Keyword(s):  
Potassium Chloride ◽  
Dura Mater ◽  
Paranasal Sinuses ◽  
Interstitial Fluid ◽  
Receptive Fields ◽  
Nasal Bone ◽  
Afferent Input ◽  
Noxious Stimulation ◽  
Trigeminal Neurons ◽  
Stimulation Of

Background The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses. Methods In isoflurane anaesthetised rats, extracellular recordings were made from neurons in the spinal trigeminal nucleus with afferent input from the exposed frontal dura mater. Dural and facial receptive fields were mapped and the paranasal cavities below the thinned nasal bone were stimulated by sequential application of synthetic interstitial fluid, 40 mM potassium chloride, 100 µM bradykinin, 1% ethanol (vehicle) and 100 µm capsaicin. Results Twenty-five neurons with input from the frontal dura mater and responses to chemical stimulation of the paranasal cavities were identified. Some of these neurons had additional receptive fields in the parietal dura, most of them in the face. The administration of synthetic interstitial fluid, potassium chloride and ethanol was not followed by significant changes in activity, but bradykinin provoked a cluster of action potentials in 20 and capsaicin in 23 neurons. Conclusion Specific spinal trigeminal neurons with afferent input from the cranial dura mater respond to stimulation of paranasal cavities with noxious agents like bradykinin and capsaicin. This pattern of activation may be due to convergent input of trigeminal afferents that innervate dura mater and nasal cavities and project to spinal trigeminal neurons, which could explain the genesis of headaches due to disorders of paranasal sinuses.

Lateral cervical nucleus in the cat: functional organization and characteristics

1978 ◽  
Vol 41 (6) ◽  
pp. 1511-1534 ◽  
Author(s):  
A. D. Craig ◽  
D. N. Tapper
Keyword(s):  
Receptive Field ◽  
Receptive Fields ◽  
Dorsal Column ◽  
Receptor Type ◽  
Noxious Stimulation ◽  
Type I ◽  
Medial Lemniscus ◽  
Dorsal Column Nuclei ◽  
Lateral Cervical Nucleus ◽  
Stimulation Of

1. The lateral cervical nucleus (LCN) was investigated with extracellular recordings in the anesthetized cat. A total of 556 LCN units were characterized; the locations of most of these were histologically verified. Half of these had receptive fields on the rostral third of the ipsilateral body surface including the face; 14% had fields on the thorax or abdomen, 33% had fields on the hindlimb or tail, and about 3% had receptive fields larger than one limb. 2. The LCN was observed to be somatotopically organized in experiments using angled microelectrode penetrations. Hindlimb units were dorsolateral, forelimb units ventromedial, and face units most medial within the LCN. In regions where LCN cells were present only in the medial portion of the dorsolateral funiculus, they were all forelimb units. 3. A special subpopulation (17%) of cells were clustered most ventromedially in the LCN. These units had large or disjoint receptive fields, and/or responded to deep, visceral, or noxious stimulation. A third of these did not project in the medial lemniscus (ML); many were synaptically activated by stimulation of the ML. Those that did project in the ML had significantly longer latencies than all other LCN units. It is suggested that this subpopulation contains local LCN interneurons. 4. The specific mechanoreceptor inputs were identified for each of 121 projecting LCN units. Receptor inputs were uniform across each receptive field; that is, each unit that responded to a given receptor type was observed to respond to receptors of that type throughout its receptive field. Input from large-fiber-diameter, velocity-sensitive mechanoreceptors was predominant. The absence of input from slowly adapting type I and II receptors and from joint receptors was confirmed. A significant number of units (17.3%) could be driven by only one receptor type. The LCN sample profile agrees closely with the receptor representation in the hindlimb portion of the spinocervical tract. It is concluded that these data that anatomic specification of convergence occurs in the LCN with respect to receptor connectivity, and that this specification originates in lamina IV of the dorsal horn. 5. Stimulation of the dorsal column nuclei synaptically excited 23% of the LCN units tested. In two cases it was possible to demonstrate, by collision, that this occurred via collaterals of spinocervical tract axons. It is concluded that some spinocervical axons have collaterals terminating in the rostral parts of the dorsal column nuclei.

Structure-function relationships in rat medullary and cervical dorsal horns. II. Medullary dorsal horn cells

1986 ◽  
Vol 55 (6) ◽  
pp. 1187-1201 ◽  
Author(s):  
W. E. Renehan ◽  
M. F. Jacquin ◽  
R. D. Mooney ◽  
R. W. Rhoades
Keyword(s):  
Receptive Field ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Noxious Stimulation ◽  
Medial Lemniscus ◽  
Guard Hair ◽  
Primary Afferent ◽  
Medullary Dorsal Horn ◽  
Low Threshold

In Nembutal-anesthetized rats, 31 physiologically identified medullary dorsal horn (MDH) cells were labeled with horseradish peroxidase (HRP). Ten responded only to deflection of one or more vibrissae. Six cells were activated by guard hair movement only, six by deflection of guard hairs or vibrissa(e), and seven by pinch of facial skin with serrated forceps. Different classes of low-threshold cells could not be distinguished on the basis of their somadendritic morphologies or laminar distribution. Neurons activated by multiple vibrissae were unique, however, in that one sent its axon into the medial lemniscus, and three projected into the trigeminal spinal tract. None of the guard hair-only or vibrissae-plus-guard hair neurons had such projections. Cells that responded best to noxious stimulation were located mainly in laminae I, II, and deep V, while neurons activated by vibrissa(e) and/or guard hair deflection were located in layers III, IV, and superficial V. Low-threshold neurons generally had fairly thick dendrites with few spines, whereas high-threshold cells tended to have thinner dendrites with numerous spines. Moreover, the dendritic arbors of low-threshold cells were, for the most part, denser than those of the noxious cells. Neurons with mandibular receptive fields were located in the dorsomedial portion of the MDH; cells with ophthalmic fields were found in the ventrolateral MDH, and maxillary cells were interposed. Cells sensitive to deflection of dorsal mystacial vibrissae and/or guard hairs were located ventral to those activated by more ventral hairs. Neurons with rostral receptive fields were found in the rostral MDH, while cells activated by hairs of the caudal mystacial pad, periauricular, and periorbital regions were located in the caudal MDH. Receptive-field types were encountered that have not been reported for trigeminal primary afferent neurons: multiple vibrissae; vibrissae plus guard hairs; and wide dynamic range. The latter two can be explained by the convergence of different primary afferent types onto individual neurons. Our failure to find a significant relationship between dendritic area (in the transverse plane) and the number of vibrissae suggests that primary afferent convergence may not be responsible for the synthesis of the multiple vibrissae receptive field. Excitatory connections between MDH neurons may, therefore, account for multiple vibrissae receptive fields in the MDH.

Responses of neurons in primate ventral posterior lateral nucleus to noxious stimuli

1980 ◽  
Vol 43 (6) ◽  
pp. 1594-1614 ◽  
Author(s):  
D. R. Kenshalo ◽  
G. J. Giesler ◽  
R. B. Leonard ◽  
W. D. Willis
Keyword(s):  
Receptive Fields ◽  
Dorsal Column ◽  
Sensory Cortex ◽  
Noxious Stimulation ◽  
Mechanical Stimuli ◽  
Thalamic Neuron ◽  
Noxious Heat ◽  
Thalamic Neurons ◽  
Noxious Stimuli ◽  
Stimulation Of

1. Recordings were made from the caudal part of the ventral posterior lateral (VPLc) nucleus of the thalamus in anesthetized macaque monkeys. In additon to many neurons that responded only to weak mechanical stimuli, scattered neurons were found that responded to both innocuous and noxious stimulation or just to noxious stimulation of the skin. A total of 73 such neurons were examined in 26 animals. 2. Noxious stimuli included strong mechanical stimuli (pressure, pinch, and squeezing with forceps) and graded noxious heat (from 35 degrees C adapting temperature to 43, 45, 47, and 50 degrees C). The responses of the VPLc neurons increased progressively with greater intensities of noxious stimulation. The stimulus-response function when noxious heat stimuli were used was a power function with an exponent greater than one. 3. Repetition of the noxious heat stimuli revealed sensitization of the responses of the thalamic neurons to such stimuli. The threshold for a response to noxious heat was lowered, and the responses to supra-threshold noxious heat stimuli were enhanced. 4. The responses of VPLc neurons to noxious heat stimuli adapted after reaching a peak discharge frequency. The rate of adaptation was slower for a stimulus of 50 degrees C than for one of 47 degrees C. 5. For the six neurons tested, responses to noxious heat were dependent on pathways ascending in the ventral part of the lateral funiculus contralateral to the receptive field (ipsilateral to the thalamic neuron). In two cases, the input to the thalamic neurons from axons of the dorsal column was also conveyed by way of a crossed pathway in the opposite ventral quadrant. In another case, access to the thalamic neuron by way of ascending dorsal column fibers was demonstrated. 6. The thalamic neurons had restricted contralateral receptive fields that were somatotopically organized. Neurons with receptive fields on the hindlimb were in the lateral part of the VPLc nucleus, whereas neurons with receptive fields on the forelimb were in medial VPLc. 7. Ninety percent of the VPLc neurons tested that responded to noxious stimuli could be activated antidromically by stimulation of the surface of SI sensory cortex. It was possible to confirm that many of these cells project to the SI sensory cortex by using microstimulation. Successful microstimulation points were either within the SI cortex or in the white matter just beneath the cortex. 8. We conclude that some neurons in the VPLc nucleus are capable of signaling noiceptive stimuli. The nociceptive information appears to reach these cells through the ventral part of the lateral funiculus on the side contralateral to the receptive field, presumably by way of the spinothalamic tract. The VPLc cells are somatotopically organized, and they are thalamocortical neurons that project to the VPLc nucleus and SI cortex play a role in nociception.

scholarly journals Dorsal horn CGRP-expressing interneurons contribute to nerve injury-induced mechanical hypersensitivity

2020 ◽  
Author(s):  
LS Löken ◽  
A Etlin ◽  
M Bernstein ◽  
M Steyert ◽  
J Kuhn ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Spinal Cord Dorsal Horn ◽  
Noxious Stimulation ◽  
Mechanical Hypersensitivity ◽  
Peripheral Nerve Damage ◽  
Calcitonin Gene ◽  
Spinal Cord Dorsal ◽  
Stimulation Of

AbstractPrimary sensory neurons are generally considered the only source of dorsal horn calcitonin gene-related peptide (CGRP), a neuropeptide critical to the transmission of pain messages. Using a tamoxifen-inducible CGRPCreER transgenic mouse, here we identified a distinct population of CGRP-expressing excitatory interneurons in lamina III of the spinal cord dorsal horn and trigeminal nucleus caudalis. These interneurons have spine-laden, dorsally-directed, dendrites and ventrally-directed axons. Neither innocuous nor noxious stimulation provoked significant Fos expression in these neurons. However, synchronous, electrical non-nociceptive Aβ primary afferent stimulation of dorsal roots depolarized the CGRP interneurons, consistent with their receipt of a VGLUT1 innervation. In contrast, chemogenetic activation produced a significant mechanical hypersensitivity. Importantly, the CGRP interneurons could be activated after peripheral nerve injury, but only with concurrent innocuous, brush stimulation. These findings suggest that hyperexcitability of dorsal horn CGRP interneurons is an important contributor to the circuits that render touch painful after peripheral nerve damage.

scholarly journals Contribution of dorsal horn CGRP-expressing interneurons to mechanical sensitivity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Line S Löken ◽  
Joao M Braz ◽  
Alexander Etlin ◽  
Mahsa Sadeghi ◽  
Mollie Bernstein ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Nerve Injury ◽  
Spinal Cord Dorsal Horn ◽  
Noxious Stimulation ◽  
Mechanical Sensitivity ◽  
Distinct Population ◽  
Calcitonin Gene ◽  
Spinal Cord Dorsal ◽  
Fos Expression ◽  
Stimulation Of

Primary sensory neurons are generally considered the only source of dorsal horn calcitonin gene-related peptide (CGRP), a neuropeptide critical to the transmission of pain messages. Using a tamoxifen-inducible CalcaCreER transgenic mouse, here we identified a distinct population of CGRP-expressing excitatory interneurons in lamina III of the spinal cord dorsal horn and trigeminal nucleus caudalis. These interneurons have spine-laden, dorsally-directed, dendrites and ventrally-directed axons. As under resting conditions, CGRP interneurons are under tonic inhibitory control, neither innocuous nor noxious stimulation provoked significant Fos expression in these neurons. However, synchronous, electrical non-nociceptive Aβ primary afferent stimulation of dorsal roots depolarized the CGRP interneurons, consistent with their receipt of a VGLUT1 innervation. On the other hand, chemogenetic activation of the neurons produced a mechanical hypersensitivity in response to von Frey stimulation whereas their caspase-mediated ablation led to mechanical hyposensitivity. Finally, after partial peripheral nerve injury, innocuous stimulation (brush) induced significant Fos expression in the CGRP interneurons. These findings suggest that CGRP interneurons become hyperexcitable and contribute either to ascending circuits originating in deep dorsal horn or to the reflex circuits in baseline conditions, but not in the setting of nerve injury.

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