Neurons of the Dopaminergic/Calcitonin Gene-Related Peptide A11 Cell Group Modulate Neuronal Firing in the Trigeminocervical Complex: An Electrophysiological and Immunohistochemical Study

Charbit, Annabelle R; Akerman, Simon; Holland, Philip R.; Goadsby, PJ

doi:10.1523/jneurosci.2887-09.2009

Cited by 110 publications

(109 citation statements)

References 70 publications

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“…In rodent models, dopamine can block nociceptive signal transmission at the level of the trigeminocervical complex by binding D2-like receptors [43]. Also, trigeminal nociceptive transmission is influenced by the dopaminergic A11 nucleus [44]. Other key players in dopamine metabolism have also been shown to affect pain modulation.…”

Section: Discussionmentioning

confidence: 99%

Hormonally modulated migraine is associated with single-nucleotide polymorphisms within genes involved in dopamine metabolism

Sullivan¹,

Atkinson²,

Cutrer³

2013

OJGen

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Migraine is a complex trait in which multiple genetic loci, as well as environmental factors, likely contribute to its clinical manifestation. Many genetic associations reported in previous studies either have not been replicated to date or showed only marginal statistical significance, possibly due to the genetic heterogeneity of the common forms of migraine. One major phenotypic and possibly genetically identifiable migraine subgroup consists of women whose attacks are influenced by fluctuation in gonadal hormones. We hypothesized that for these women, the association between migraine attacks and the menstrual cycle might be attributable to an increased prevalence of genetic polymorphisms in the hypothalamic-pituitary-gonadal axis. We selected 21 such polymerphisms previously reported to be associated with the common forms of migraine and genotyped 1740 individuals (1132 migraineurs) to determine whether any of these selected polymorphisms occurred more frequently in females with hormonally modulated migraine. We were able to confirm the association of migraine with 3 genetic polymorphisms seen in previous studies (rs4680

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Section: Discussionmentioning

confidence: 99%

Hormonally modulated migraine is associated with single-nucleotide polymorphisms within genes involved in dopamine metabolism

Sullivan¹,

Atkinson²,

Cutrer³

2013

OJGen

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“…Dopamine-like immunoreactivity is profusely distributed throughout the gray matter of the spinal dorsal horn [31], and all 5 G-protein-coupled receptor types through which synaptic effects of dopamine are exerted, namely D1 through D5, have been found in the spinal cord [12,19,22,44,61,68,77,78]. The A11 region in the dorsal posterior hypothalamus is the sole known source of dopaminergic innervation to the dorsal horn [30,62], and diencephalospinal projections arising from these neurons inhibit nociceptive transmission at the dorsal horn level, primarily via D2 receptors [19,24,40,64,65]. Studies show that D2R may establish complex interactions with opioid receptors, as D2R-agonists have so far been linked to both facilitation [55] and attenuation [34] of opioid analgesia, whereas D2R-blockade may reportedly potentiate [60] or diminish [55] MOR analgesia.…”

Section: Introductionmentioning

confidence: 99%

Synaptic upregulation and superadditive interaction of dopamine D2- and μ-opioid receptors after peripheral nerve injury

Aira¹,

Barrenetxea²,

Buesa³

et al. 2014

Pain

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A sound strategy for improving the clinical efficacy of opioids involves exploiting positive interactions with drugs directed at other targets in pain pathways. The current study investigated the role of dopamine receptor D2 (D2R) in modulation of spinal dorsal horn excitability to noxious input, and interactions therein with μ-opioid receptor (MOR) in an animal model of neuropathic pain induced by spinal nerve ligation (SNL). C-fiber-evoked field potentials in the spinal dorsal horn were depressed concentration dependently by spinal superfusion with the D2R agonist quinpirole both in nerve-injured and sham-operated (control) rats. However, quinpirole-induced depression was significant at 10 μmol/L after SNL but only at 100 μmol/L in control rats. This quinpirole effect was completely abolished by MOR antagonist CTOP at subclinical concentration (1 μmol/L) in nerve-injured rats, but was unaltered in sham-operated rats. Nine days after SNL, D2R was upregulated to both presynaptic and postsynaptic locations in dorsal horn neurons, as revealed by double confocal immunofluorescence stainings for synaptophysin and PSD-95. In addition, D2R/MOR co-localization was increased after SNL. Co-administration of 1 μmol/L quinpirole, insufficient per se to alter evoked potentials, dramatically enhanced inhibition of evoked potentials by MOR agonist DAMGO, reducing the IC50 value of DAMGO by 2 orders of magnitude. The present data provide evidence of profound functional and subcellular changes in D2R-mediated modulation of noxious input after nerve injury, including positive interactions with spinal MOR. These results suggest D2R co-stimulation as a potential avenue to improve MOR analgesia in sustained pain states involving peripheral nerve injury.

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“…Note that a large number of intensely GAD-IR processes were observed in the hypothalamus (ventral) region including A11, and more weakly GAD-IR processes were present in the thalamus (dorsal). The delimited areas in a-c are shown at higher magnification in d- ◂ [2,4,5,33]. In these previous studies, it was also reported that there were projections to the spinal cord derived from both non-TH and TH neurons of the A11 region.…”

Section: Projection To the Spinal Cordmentioning

confidence: 78%

“…Dopaminergic neurons are enriched in several brain regions designated as A8-A16 [1]. Among these, the A11 dopaminergic system is the only dopaminergic system that gives rise to descending projections to the spinal cord [2,4,5]. In addition to these particular neural connections, the fact that dopaminergic receptors are present in the spinal cord, and that dopamine receptor agonists alleviate the symptoms of restless legs syndrome (RLS), led to the hypothesis that hypo-activity of A11 neurons is a contributing factor in the pathogenesis of RLS [3].…”

Section: Introductionmentioning

confidence: 99%

Three Types of A11 Neurons Project to the Rat Spinal Cord

et al. 2017

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The A11 dopaminergic cell group is the only group among the A8-A16 dopaminergic cell groups that includes neurons innervating the spinal cord, and a decrease in dopaminergic transmission at the spinal cord is thought to contribute to the pathogenesis of restless legs syndrome. However, the mechanisms regulating the neuronal activity of A11 dopaminergic neurons remain to be elucidated. Unraveling the neuronal composition, distribution and connectivity of A11 neurons would provide insights into the mechanisms regulating the spinal dopaminergic system. To address this, we performed immunohistochemistry for calcium-binding proteins such as calbindin (Calb) and parvalbumin (PV), in combination with the retrograde tracer Fluorogold (FG) injected into the spinal cord. Immunohistochemistry for Calb, PV, or tyrosine hydroxylase (TH), a marker for dopaminergic neurons, revealed that there were at least three types of neurons in the A11 region: neurons expressing Calb, TH, or both TH and Calb, whereas there were no PV-immunoreactive (IR) cell bodies. Both Calb- and PV-IR processes were found throughout the entire A11 region, extending in varied directions depending on the level relative to bregma. We found retrogradely labeled FG-positive neurons expressing TH, Calb, or both TH and Calb, as well as FG-positive neurons lacking both TH and Calb. These findings indicate that the A11 region is composed of a variety of neurons that are distinct in their neurochemical properties, and suggest that the diencephalospinal dopamine system may be regulated at the A11region by both Calb-IR and PV-IR processes, and at the terminal region of the spinal cord by Calb-IR processes derived from the A11 region.

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Neurons of the Dopaminergic/Calcitonin Gene-Related Peptide A11 Cell Group Modulate Neuronal Firing in the Trigeminocervical Complex: An Electrophysiological and Immunohistochemical Study

Cited by 110 publications

References 70 publications

Hormonally modulated migraine is associated with single-nucleotide polymorphisms within genes involved in dopamine metabolism

Hormonally modulated migraine is associated with single-nucleotide polymorphisms within genes involved in dopamine metabolism

Synaptic upregulation and superadditive interaction of dopamine D2- and μ-opioid receptors after peripheral nerve injury

Three Types of A11 Neurons Project to the Rat Spinal Cord

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