BookID 152647_Canning_ChapID 10_Proof# 1 - 27/3/09 Purines and Sensory Nerves 1 Geoffrey Burnstock 2 Contents 3 1 Introduction .. ............................................................................... 00 4 2 Peripheral Sensory Ganglionic Neurons .................................................... 00 5 2.1 Dorsal Root Ganglia .................................................................. 00 6 2.2 Nodose Ganglia ....................................................................... 00 7 2.3 Trigeminal Ganglia ................................................................... 00 8 2.4 Petrosal Ganglia ....................................................................... 00 9 2.5 Retinal Ganglia ........................................................................ 00 10 2.6 Intramural Enteric Sensory Neurons .................................................. 00 11 3 Peripheral Sensory Nerve Terminals ....................................................... 00 12 3.1 Carotid Body .......................................................................... 00 13 3.2 Lung ................................................................................... 00 14 3.3 Gut ..................................................................................... 00 15 3.4 Urinary Bladder ....................................................................... 00 16 3.5 Inner Ear .............................................................................. 00 17 3.6 Eye .................................................................................... 00 18 3.7 Nasal Organ ........................................................................... 00 19 3.8 Taste Buds ............................................................................. 00 20 3.9 Skin, Muscle and Joints ............................................................... 00 21 3.10 Heart ................................................................................... 00 22 4 Central Sensory Nerves ..................................................................... 00 23 4.1 Spinal Cord ............................................................................ 00 24 4.2 Nucleus Tractus Solitarius ............................................................ 00 25 4.3 Ventrolateral Medulla ................................................................. 00 26 4.4 Sensory Nuclei ........................................................................ 00 27 4.5 Trigeminal Mesencephalic Nucleus .................................................. 00 28 4.6 Locus Coeruleus ...................................................................... 00 29 4.7 Area Postrema ......................................................................... 00 30 4.8 HypothalamusUncorrected......................................................................... Proof 00 31 5 Purinergic Mechanosensory Transduction .................................................. 00 32 G. Burnstock Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill Street, London, NW3 2PF, UK [email protected] B.J. Canning and D. Spina (eds.), Sensory Nerves, Handbook of Experimental Pharmacology 194, DOI: 10.1007/978‐3‐540‐79090‐7_10, # Springer‐Verlag Berlin Heidelberg 2009 BookID 152647_Canning_ChapID 10_Proof# 1 - 27/3/09 G. Burnstock 33 5.1 Urinary Bladder ....................................................................... 00 34 5.2 Ureter ... ............................................................................... 00 35 5.3 Gut ..................................................................................... 00 36 5.4 Uterus .. ............................................................................... 00 37 5.5 Tooth Pulp ............................................................................. 00 38 5.6 Tongue . ............................................................................... 00 39 5.7 Skin and Joints ........................................................................ 00 40 6 Purinergic Sensory Pathology ............................................................... 00 41 6.1 Pain .................................................................................... 00 42 6.2 Migraine ............................................................................... 00 43 6.3 Diseases of Special Senses ............................................................ 00 44 6.4 Bladder Diseases ...................................................................... 00 45 6.5 Gut Disorders ......................................................................... 00 46 6.6 Arthritis . ............................................................................... 00 47 6.7 Respiratory Diseases .................................................................. 00 48 6.8 Central Disorders ...................................................................... 00 49 7 Development of Purinergic Sensory Signalling ............................................ 00 50 8 Evolution of Purinergic Sensory Mechanisms .............................................. 00 51 9 Concluding Comments ...................................................................... 00 52 References ....................................................................................... 00 53 54 Abstract P2X and P2Y nucleotide receptors are described on sensory neurons and 55 their peripheral and central terminals in dorsal root, nodose, trigeminal, petrosal, 56 retinal and enteric ganglia. Peripheral terminals are activated by ATP released from 57 local cells by mechanical deformation, hypoxia or various local agents in the 58 carotid body, lung, gut, bladder, inner ear, eye, nasal organ, taste buds, skin, muscle 59 and joints mediating reflex responses and nociception. Purinergic receptors on 60 fibres in the dorsal spinal cord and brain stem are involved in reflex control of 61 visceral and cardiovascular activity, as well as relaying nociceptive impulses to 62 pain centres. Purinergic mechanisms are enhanced in inflammatory conditions and 63 may be involved in migraine, pain, diseases of the special senses, bladder and gut, 64 and the possibility that they are also implicated in arthritis, respiratory disorders and 65 some central nervous system disorders is discussed. Finally, the development and 66 evolution of purinergic sensory mechanisms are considered. 67 Keywords Bladder, Brain stem, Carotid body, Ganglion, Gut 68 1 IntroductionUncorrected Proof 69 Review articles have been published concerned with P2X and P2Y receptors 70 in sensory neurons (Burnstock 2000, 2007; Tsuda and Inoue 2006), purinergic 71 sensory-motor neurotransmission (Rubino and Burnstock 1996) and purine-mediated 72 signalling in pain (Burnstock and Wood 1996; Burnstock1996a, b, 2001a, 2006; Au1 73 McGaraughty and Jarvis 2006; Shieh et al. 2006; Inoue 2007). BookID 152647_Canning_ChapID 10_Proof# 1 - 27/3/09 Purines and Sensory Nerves The first hint that ATP might be a neurotransmitter arose when it was proposed 74 that ATP released from sensory nerve collaterals during antidromic nerve stimula- 75 tion of the great auricular nerve caused vasodilatation of the rabbit ear artery 76 (Holton 1959). ATP was shown early to excite mammalian dorsal root ganglia 77 (DRG) neurons and some neurons in the dorsal horn of the spinal cord (Krishtal 78 et al. 1983; Jahr and Jessell 1983). Extracellular ATP was reported early to produce 79 pain sensation in humans (Collier et al. 1966; Bleehen and Keele 1977) and to 80 participate in pain pathways in the spinal cord (Fyffe and Perl 1984; Salter and 81 Henry 1985). 82 Recent reviews about the current status of and pharmacological characteriza- 83 tion of subtypes of receptors for purines and pyrimidines are available, including 84 four subtypes of P1 (adenosine), seven subtypes of P2X ionotropic and eight 85 subtypes of P2Y metabotropic receptors (North 2002; Abbracchio et al. 2006). A 86 landmark discovery related to this chapter was the cloning of P2X3 receptors and 87 their localization on sensory nerves in 1995 (Lewis et al. 1995; Chen et al. 1995a, 88 Au2 b). All P2X subtypes, except P2X7, are found in sensory neurons, although the P2X3 89 receptor has the highest level of expression [in terms of both messenger RNA 90 (mRNA) and protein] and P2X2/3 heteromultimers are particularly prominent in the 91 nodose ganglion. P2X3 and P2X2/3 receptors are expressed on isolectin B4 (IB4) 92 binding subpopulations of small nociceptive neurons (Bradbury et al. 1998). P2Y 93 receptors are also present on sensory neurons sometimes coexpressed with P2X3 94 receptors (Burnstock 2007). It has been suggested that while P2X3 receptor activa- 95 tion leads to increased firing of DRG neurons and subsequently to increased release 96 of sensory transmitter from their central processes, P2Y1 receptor activation may 97 decrease the release of sensory transmitter onto spinal cord neurons and may 98 thereby partly counterbalance the excitatory effect of ATP. 99 2 Peripheral Sensory Ganglionic Neurons 100 There have been many reports characterizing the native P2X receptors in sensory 101 neurons, including those from DRG, trigeminal, nodose, petrosal and enteric gang- 102 lia (Burnstock 2000, 2007; Dunn et al. 2001). DRG and trigeminal ganglia contain 103 primary somatosensory neurons, receiving nociceptive, mechanical and proprio- 104 ceptive inputs. Nodose and petrosal ganglia, on the other hand, contain cell bodies 105 of afferents to visceral organs. 106 All P2X subtypes,Uncorrected