Pain
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Odontoblasts form the outermost cellular layer of the dental pulp where they have been proposed to act as sensory receptor cells. Despite this suggestion, evidence supporting their direct role in mediating thermo-sensation and nociception is lacking. Transient receptor potential (TRP) ion channels directly mediate nociceptive functions, but their functional expression in human odontoblasts has yet to be elucidated. ⋯ Using a gene silencing approached we further confirmed a role for TRPA1 in mediating noxious cold responses in odontoblasts. We conclude that human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth. Cultured and native human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth.
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Both serotonergic and dopaminergic receptor modulation can alter trigeminal nociceptive processing, and descending A11 dopaminergic projections can affect trigeminal nociceptive transmission. Here we aimed to test the interaction between dopamine D(2) and serotonin 5-HT(1B/1D) receptors and their individual and combined effects in order to better understand the relationship of the descending influences of these systems on nociceptive trigeminovascular afferents. Extracellular recordings were made in the rat trigeminocervical complex in response to electrical stimulation of the dura mater and mechanical noxious and innocuous stimulation of the ipsilateral ophthalmic dermatome. ⋯ Both naratriptan alone, and quinpirole combined with GR127935, inhibited firing in the trigeminocervical complex evoked by noxious stimuli, returning it to prelesion baseline, while the response to innocuous stimuli remained facilitated. Immunohistochemical staining demonstrated D(2)-receptor and 5-HT(1B/1D)-receptor colocalization in the trigeminocervical complex. The data suggest that the serotonergic and dopaminergic antinociceptive pathways act simultaneously on neurons in the trigeminocervical complex, and both amine systems need to be functioning for trigeminal sensitization to be reversed.
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Comparative Study
Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder.
Activation of extracellular signal-regulated kinases (ERK) 1/2 in dorsal horn neurons is important for the development of somatic hypersensitivity and spinal central sensitization after peripheral inflammation. However, data regarding the roles of spinal ERK1/2 in the development of visceral hyperalgesia are sparse. Here we studied the activation of ERK1/2 in the lumbosacral spinal cord after innocuous and noxious distention of the inflamed (cyclophosphamide-treated) and noninflamed urinary bladder in mice. ⋯ Functional blockade of spinal ERK1/2 activity via intrathecal administration of the upstream MEK inhibitor U0126 attenuated distention-evoked bladder nociception and caused a significant downward shift of the VMR stimulus-response curve. In summary, we have provided functional and immunohistochemical evidence that activation of lumbosacral spinal ERK1/2 is associated with the development of primary visceral (bladder) hyperalgesia. Our results suggest that aberrant processing of visceral nociceptive information at the level of the lumbosacral spinal cord via activation of ERK1/2 signaling may contribute to chronic bladder pain in the context of inflammation.
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Somatoform disorders are characterized by the presence of multiple somatic symptoms. Patients often experience different pain syndromes, and recent research suggests that sympathovagal balance is disturbed in somatoform patients, which could be related to alteration in pain sensitivity. This study analyzed how proposed sympathovagal imbalance interacts with objective pain assessment and the imagination of pain in somatoform disorders. ⋯ We conclude that our data demonstrate an imbalance in sympathovagal activation and a hyposensitivity to pain tolerance stimuli in somatoform disorders. Parasympathetic reactivity might form crucial information when judging pain-associated affective-motivational components. Our results might be attributable to a deficient detection of visceral signals and might be a pathogenetic mechanism for the development of emotional difficulties and increased everyday vulnerability in somatoform patients.