Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the trigeminovascular pain signalling system appears involved in migraine pathophysiology. However, the molecular mechanisms are only partially known. Stimulation of cAMP and cGMP production as well as inhibition of their breakdown induce migraine-like headache. Additionally, migraine may be associated with mutations in ion channels. The aim of the present study was to describe the expression of phosphodiesterase 3 (PDE3) and 5 (PDE5) and cyclic nucleotide-gated ion channels (CNG) in cerebral arteries, meninges, and the trigeminal ganglion. mRNA for PDE and CNG was determined in the rat middle cerebral artery, basilar artery, trigeminal ganglion, and dura mater using real-time PCR. PDE and CNG proteins were identified using Western blot. For comparison, rat aorta and mesenteric artery were analysed. PDE3A, PDE3B, and PDE5A mRNA were detected in all tissues examined except for PDE3A mRNA in dura mater and the trigeminal ganglion. PDE5A and PDE3A protein expression was present in both cerebral and peripheral arteries, whereas PDE3B protein was present only in the cerebral arteries. The CNGA4 and B1 subunit mRNAs were detected in cerebral arteries and CNGA2 also in the mesenteric artery. CNGA2 and A3 proteins were found in cerebral arteries and dura and CNGA1, CNGA2 and CNGA3 in the trigeminal ganglion. In conclusion, PDE3A, PDE3B, PDE5A, and five CNG subunits were expressed in several components of the trigeminovascular system of the rat. This suggests that modulation of cAMP and cGMP levels by PDE and activation of CNG may play a role in trigeminovascular pain signalling leading to migraine headache.
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PMID:Phosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in rat trigeminovascular system. 1680 96

A large body of evidence indicates that nitric oxide (NO) and cGMP contribute to central sensitization of pain pathways during inflammatory pain. Here, we investigated the distribution of cyclic nucleotide-gated (CNG) channels in the spinal cord, and identified the CNG channel subunit CNGA3 as a putative cGMP target in nociceptive processing. In situ hybridization revealed that CNGA3 is localized to inhibitory neurons of the dorsal horn of the spinal cord, whereas its distribution in dorsal root ganglia is restricted to non-neuronal cells. CNGA3 expression is upregulated in the superficial dorsal horn of the mouse spinal cord and in dorsal root ganglia following hindpaw inflammation evoked by zymosan. Mice lacking CNGA3 (CNGA3(-/-) mice) exhibited an increased nociceptive behavior in models of inflammatory pain, whereas their behavior in models of acute or neuropathic pain was normal. Moreover, CNGA3(-/-) mice developed an exaggerated pain hypersensitivity induced by intrathecal administration of cGMP analogs or NO donors. Our results provide evidence that CNGA3 contributes in an inhibitory manner to the central sensitization of pain pathways during inflammatory pain as a target of NO/cGMP signaling.
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PMID:CNGA3: a target of spinal nitric oxide/cGMP signaling and modulator of inflammatory pain hypersensitivity. 2181 79

Cyclic nucleotide-gated (CNG) channels, which are directly activated by cAMP and cGMP, have long been known to play a key role in retinal and olfactory signal transduction. Emerging evidence indicates that CNG channels are also involved in signaling pathways important for pain processing. Here, we found that the expression of the channel subunits CNGA2, CNGA3, CNGA4 and CNGB1 in dorsal root ganglia, and of CNGA2 in the spinal cord, is transiently altered after peripheral nerve injury in mice. Specifically, we show using in situ hybridization and quantitative real-time RT-PCR that CNG channels containing the CNGB1b subunit are localized to populations of sensory neurons and predominantly excitatory interneurons in the spinal dorsal horn. In CNGB1 knockout (CNGB1-/-) mice, neuropathic pain behavior is considerably attenuated whereas inflammatory pain behavior is normal. Finally, we provide evidence to support CNGB1 as a downstream mediator of cAMP signaling in pain pathways. Altogether, our data suggest that CNGB1-positive CNG channels specifically contribute to neuropathic pain processing after peripheral nerve injury.
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PMID:Neuropathic and cAMP-induced pain behavior is ameliorated in mice lacking CNGB1. 3227 40

The detection of ambient cold is critical for mammals, who use this information to avoid tissue damage by cold and to maintain stable body temperature. The transduction of information about the environmental cold is mediated by cold-sensitive ion channels expressed in peripheral sensory nerve endings in the skin. Most transduction mechanisms for detecting temperature changes identified to date depend on transient receptor potential (TRP) ion channels. Mild cooling is detected by the menthol-sensitive TRPM8 ion channel, but how painful cold is detected remains unclear. The TRPA1 ion channel, which is activated by cold in expression systems, seemed to provide an answer to this question, but whether TRPA1 is activated by cold in neurons and contributes to the sensation of cold pain continues to be a matter of debate. Recent advances have been made in this area of investigation with the identification of several potential cold-sensitive ion channels in thermosensory neurons, including two-pore domain potassium channels (K2P), GluK2 glutamate receptors, and CNGA3 cyclic nucleotide-gated ion channels. This mini-review gives a brief overview of the way by which ion channels contribute to cold sensation, discusses the controversy around the cold-sensitivity of TRPA1, and provides an assessment of some recently-proposed novel cold-transduction mechanisms. Evidence for another unidentified cold-transduction mechanism is also presented.
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PMID:The Role of Cold-Sensitive Ion Channels in Peripheral Thermosensation. 3297 56