Fos expression in the medullary dorsal horn of the rat after chronic constriction injury to the infraorbital nerve

Craniofacial neuropathic pain affects millions of people worldwide and is often difficult to treat. Two key mechanisms underlying this condition are a loss of the negative control exerted by inhibitory interneurons and an early microglial reaction. Basic features of these mechanisms, however, are still poorly understood. Using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic pain in mice, we have examined the changes in the expression of GAD, the synthetic enzyme of GABA, and GlyT2, the membrane transporter of glycine, as well as the microgliosis that occur at early (5 days) and late (21 days) stages post-CCI in the medullary and upper spinal dorsal horn. Our results show that CCI-IoN induces a down-regulation of GAD at both postinjury survival times, uniformly across the superficial laminae. The expression of GlyT2 showed a more discrete and heterogeneous reduction due to the basal presence in lamina III of ‘patches’ of higher expression, interspersed within a less immunoreactive ‘matrix’, which showed a more substantial reduction in the expression of GlyT2. These patches coincided with foci lacking any perceptible microglial reaction, which stood out against a more diffuse areas of strong microgliosis. These findings may provide clues to better understand the neural mechanisms underlying allodynia in neuropathic pain syndromes.

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The gap junction blocker carbenoxolone attenuates nociceptive behavior and medullary dorsal horn central sensitization induced by partial infraorbital nerve transection in rats

Pain ◽

10.1016/j.pain.2013.11.004 ◽

2014 ◽

Vol 155 (2) ◽

pp. 429-435 ◽

Cited By ~ 25

Author(s):

Hua Wang ◽

Ye Cao ◽

Chen-Yu Chiang ◽

Jonathan O. Dostrovsky ◽

Barry J. Sessle

Keyword(s):

Gap Junction ◽

Dorsal Horn ◽

Central Sensitization ◽

Infraorbital Nerve ◽

Nerve Transection ◽

Nociceptive Behavior ◽

Medullary Dorsal Horn

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Fos-like immunoreactivity in the superficial medullary dorsal horn induced by noxious and innocuous thermal stimulation of facial skin in the rat

Journal of Neurophysiology ◽

10.1152/jn.1993.70.5.1811 ◽

1993 ◽

Vol 70 (5) ◽

pp. 1811-1821 ◽

Cited By ~ 67

Author(s):

A. M. Strassman ◽

B. P. Vos ◽

Y. Mineta ◽

S. Naderi ◽

D. Borsook ◽

...

Keyword(s):

Dorsal Horn ◽

High Threshold ◽

Primary Afferent ◽

Lamina I ◽

Medullary Dorsal Horn ◽

Cold Receptors ◽

Warm Receptors ◽

Low Threshold ◽

Fos Expression ◽

Stimulation Of

1. To examine further the ability of different classes of nociceptive and nonnociceptive primary afferent neurons to induce c-fos expression in central neurons, fos-like immunoreactivity was examined in the medullary dorsal horn (laminae I-IV) of the rat after facial application of a range of warming and cooling thermal stimuli. Urethan-anesthetized rats received 15 30-s thermal pulses (53, 50, 47, 41, 25, or 10 degrees C) applied to the vibrissal pad over a period of 30 min and were perfused 2 h after the end of stimulation. 2. Stimulation of 41 degrees C produced no significant increase in the number of fos-LI-labeled cells in lamina I or II compared with control (35 degrees C) animals. 3. Stimulation of 47 degrees C produced a significant increase in the number of fos-LI-labeled cells in both laminae I and II. Stimulation of 50 degrees C produced a significant increase in labeling, compared with that produced by 47 degrees C, which was primarily in lamina II. Stimulation of 53 degrees C produced no further increase in the number of labeled cells, compared with that produced by 50 degrees C, in lamina I or II. 4. In the cooling direction, 25 degrees C produced a significant increase in labeling above control levels in both lamina I and II, whereas 10 degrees C produced a further increase compared with 25 degrees C, which was restricted to lamina I. 5. None of the stimuli produced a significant increase in labeling in laminae III-IV. 6. The results are interpreted as providing evidence that low-threshold cold receptors, high-threshold cold receptors, and nociceptors are capable of inducing fos expression in dorsal horn neurons, whereas warm receptors are relatively ineffective. The results also provide evidence that neurons that receive input from C polymodal nociceptors are present in both laminae I and II, as are neurons that receive input from low-threshold cold receptors. Neurons that receive input from high-threshold cold receptors, but not from low-threshold cold receptors, appear to be located preferentially in lamina I. The shape of the curve relating fos-LI labeling to stimulus temperature in the warming direction is consistent with the expected pattern of recruitment of primary afferent nociceptors.

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Microglia and Inhibitory Circuitry in the Medullary Dorsal Horn: Laminar and Time-Dependent Changes in a Trigeminal Model of Neuropathic Pain

International Journal of Molecular Sciences ◽

10.3390/ijms22094564 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4564

Author(s):

Nuria García-Magro ◽

Yasmina B. Martin ◽

Pilar Negredo ◽

Francisco Zafra ◽

Carlos Avendaño

Keyword(s):

Neuropathic Pain ◽

Dorsal Horn ◽

Substantial Reduction ◽

Negative Control ◽

Infraorbital Nerve ◽

Survival Times ◽

Medullary Dorsal Horn ◽

Inhibitory Circuitry ◽

Basic Features ◽

Heterogeneous Reduction

Craniofacial neuropathic pain affects millions of people worldwide and is often difficult to treat. Two key mechanisms underlying this condition are a loss of the negative control exerted by inhibitory interneurons and an early microglial reaction. Basic features of these mechanisms, however, are still poorly understood. Using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic pain in mice, we have examined the changes in the expression of GAD, the synthetic enzyme of GABA, and GlyT2, the membrane transporter of glycine, as well as the microgliosis that occur at early (5 days) and late (21 days) stages post-CCI in the medullary and upper spinal dorsal horn. Our results show that CCI-IoN induces a down-regulation of GAD at both postinjury survival times, uniformly across the superficial laminae. The expression of GlyT2 showed a more discrete and heterogeneous reduction due to the basal presence in lamina III of ‘patches’ of higher expression, interspersed within a less immunoreactive ‘matrix’, which showed a more substantial reduction in the expression of GlyT2. These patches coincided with foci lacking any perceptible microglial reaction, which stood out against a more diffuse area of strong microgliosis. These findings may provide clues to better understand the neural mechanisms underlying allodynia in neuropathic pain syndromes.

Download Full-text