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Irritant and analgesic effects of nicotine

Institution: University of California, Davis
Investigator(s): Earl Carstens, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11RT-0053 Award: $226,650
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
This project continues our studies of the irritant and analgesic (pain-reducing) effects of nicotine, an active constituent of tobacco. Nicotine has two major sensory effects. (1) Irritation or pain occurs when nicotine contacts the mouth, throat, eyes or skin. This may contribute to the liking of tobacco products (analogous to some people’s preference for spicy foods). (2) Nicotine also reduces pain by activating pain-inhibitory systems in the brain. Analgesia may contribute to addiction, and dissipation of analgesia may be cause increased discomfort during withdrawal, thus contributing to the difficulty of quitting. Studies of these divergent actions of nicotine are described below.

Nicotine Irritation. Our previous studies have shown that nicotine excites pain fibers in the oral cavity, that in turn activate the central “trigeminal” (Vc) pathway for sensations of oral pain, temperature and touch. We hypothesize that the electrical activity of Vc neurons underlies the perception of irritation, and have demonstrated correlations in the temporal pattern of Vc neuronal activity and perceived oral irritation. Nicotine-evoked irritation, and Vc firing, declines over time (“desensitization”). One aim of this proposal is to identify the specific sub-types of molecular nicotine receptors that are involved in nicotinic activation of Vc neurons. A second aim is to study the mechanism of nicotine desensitization. We will also investigate the neural basis of throat-burn sensation commonly associated with use of tobacco and cessation products. Anatomical studies will target the locations of brain neurons activated by nicotine contacting the throat. One location is the nucleus of the solitary tract (NTS), an area involved in taste and visceral functions. We will study the functional role of NTS in nicotine throat irritation as compared to the role of Vc in oral (tongue, mouth) irritation. We will also investigate the interaction between nicotine and menthol, a common additive to tobacco products that evokes both cooling and irritant sensations. A general benefit of these studies is to better understand the powerful excitatory effect of nicotine and menthol on pain (and other) sensory pathways. A practical benefit is increased understanding of how the irritant side-effects of nicotine-containing products (gum, patch, etc.) might be reduced to aid cessation. Results of these studies should increase our knowledge of why people start smoking, and why second-hand smoke is irritating.

Analgesic Effect of Nicotine. We have also shown that chronic exposure to nicotine, and cigarette smoke, causes analgesia in rats. We will continue our studies of smoke-induced analgesia to determine if it is mediated through nicotinic receptors, and/or if it represents a form of stress that induces analgesia through the central release of endorphins (endogenous opiates). Overlapping brain systems are involved in reward and analgesia, and the analgesic effect of nicotine and tobacco smoke represents an important factor in dependence. Furthermore, the analgesic effect of smoke exposure dissipates rapidly, so that the experience of increased discomfort and even pain during withdrawal from smoking contribute to relapse.
Publications

It hurts so good: oral irritation by spices and carbonated drinkds and the underlying neural mechanisms.
Periodical: Food Quality Preferences Index Medicus:
Authors: Carstens E, Iodi Carstens M, Dessirier JM, O'Mahony M, Simons CT, Sudo M, Sudo S ART
Yr: 2002 Vol: 13 Nbr: 7-8 Abs: Pg: 431-443

Intracutaneous application of pruritic and algesic chemicals elicits similar distributions of c-Fos0immunopositive neurons in rat superficial dorsal horn.
Periodical: Experimental Brain Research Index Medicus:
Authors: Jinks SL, Simons CT, Dessirier J-M, Iodi Carstens M, Antognini JF, Carstens E ART
Yr: 2002 Vol: 145 Nbr: 2 Abs: Pg: 261-269

Reduced aversion to oral capsaicin following neurotoxic destruction of superficial medullary neurons expressing NK-1 receptors.
Periodical: Brain Research Index Medicus:
Authors: Simons CT, Gogineni A, Iodi Carstens M, Carstens E ART
Yr: 2002 Vol: 945 Nbr: 1 Abs: Pg: 139-143

Sensitization of trigeminal caudalis neuronal responses to intraoral acid and salt stimuli and desensitization by nicotine.
Periodical: Pain Index Medicus:
Authors: Sudo S, Sudo M, Simons CT, Dessirier JM, Carstens E ART
Yr: 2002 Vol: 98 Nbr: 3 Abs: Pg: 277-286

Taste suppression following lingual capsaicin pretreatment in humans.
Periodical: Chemical Senses Index Medicus:
Authors: Simons CT, O'Mahony M, Carstens E ART
Yr: 2002 Vol: 27 Nbr: Abs: Pg: 353-365

Activation of brain stem neurons by irritant chemical stimulation of the throat assessed by c-fos immunohistochemistry.
Periodical: Experimental Brain Research Index Medicus:
Authors: Boucher Y, Simons CT, Cuellar JM, Jung SW, Iodi Carstns M, Carstens E ART
Yr: 2003 Vol: 148 Nbr: 2 Abs: Pg: 211-218

Suppression of central taste transmission by oral capsaicin.
Periodical: Journal of Neuroscience Index Medicus:
Authors: Simons CT, Boucher Y, Carstens E ART
Yr: 2003 Vol: 23 Nbr: 3 Abs: Pg: 978-985

Activation neurons in trigeminal caudalis by noxious oral acidic or salt stimuli is not reduced by amiloride.
Periodical: Brain Research Index Medicus:
Authors: Sudo S, Sudo M, Simons CT, Dessirier JM, Iodi Carstens M, Carstens E ART
Yr: 2003 Vol: 969 Nbr: Abs: Pg: 237-243

Trigeminal modulation of gustatory neurons in the nucleus of the solitary tract.
Periodical: Brain Research Index Medicus:
Authors: Boucher Y, Simons CT, Faurion F, Azerad J, Carstens E ART
Yr: 2003 Vol: 973 Nbr: Abs: Pg: 265-274

Lack of quinine-evoked activity in rat trigeminal subnucleus caudalis.
Periodical: Chemical Senses Index Medicus:
Authors: Simons CT, Boucher Y, Iodi Carstens M, Carstens E ART
Yr: 2003 Vol: 28 Nbr: 3 Abs: Pg: 253-259

Gustatory-irritant interactions: suppression of taste by oral capsaicin.
Periodical: Chemical Senses Index Medicus:
Authors: Boucher Y, Simons CT, Carstens E ABS
Yr: 2002 Vol: 27 Nbr: Abs: Pg: 667

Nicotine suppression of tastant-evoked neural activity in the rat.
Periodical: Chemical Senses Index Medicus:
Authors: Simons CT, Boucher Y, Carstens E ABS
Yr: 2003 Vol: 27 Nbr: Abs: Pg: 667

Activation of brain stem neurons by irritant chemical stimulation of the throat assessed by c-fos immunohistochemistry.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Cuellar JM, Boucher Y, Simons CT, Jung SW, Iodi Carstens M, Carstens E ABS
Yr: 2002 Vol: Nbr: Abs: Pg:

Nicotine suppression of tastant-evoked neural activity in the rat.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Simons CT, Boucher Y, Carstens E ABS
Yr: 2002 Vol: Nbr: Abs: Pg:

Capsaicin suppresses tastant-evoked neural activity via a peripheral mechanism.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Carstens E, Simons CT, Boucher Y ABS
Yr: 2002 Vol: Nbr: Abs: Pg:

Oral irritation by mustard oil: self-desensitization and cross-desensitization with capaicin.
Periodical: Chemical Senses Index Medicus:
Authors: Simons CT, Iodi-Carstens M, Carstens E ART
Yr: 2003 Vol: 28 Nbr: Abs: Pg: 459-465

Mecamylamine reduces nicotine cross-desensitization of trigeminal caudalis neuronal responses to oral chemical irritation.
Periodical: Brain Research Index Medicus:
Authors: Simons CT, Sudo S, Sudo M, Carstens E ART
Yr: 2003 Vol: 991 Nbr: Abs: Pg: 249-253

Mustard oil has differential effects on the response of trigeminal caudalis neurons to heat and acidity.
Periodical: Pain Index Medicus:
Authors: Simons CT, Sudo S, Sudo M, Carstens E ART
Yr: 2004 Vol: Nbr: Abs: Pg:

Antinociception induced by chronic exposure of rats to cigarette smoke.
Periodical: Neuroscience Letters Index Medicus:
Authors: Anderson KL, Pinkerton KE, Uyeminami D, Simons CT, Iodi Carstens M, Carstens E ART
Yr: 2004 Vol: Nbr: Abs: Pg:

Scratching behavior in mice with a deletion of the preprotachykinin A gene.
Periodical: Neuroscience Letters Index Medicus:
Authors: Cuellar JM, Jinks SL, Simons CT, Carstens E ART
Yr: 2003 Vol: 339 Nbr: 1 Abs: Pg: 72-76

Quantitative assessment of directed hind limb scratching behavior as a rodent itch model.
Periodical: Neuroscience Methods Index Medicus:
Authors: Nojima H, Carstens E ART
Yr: 2003 Vol: 126 Nbr: 2 Abs: Pg: 137-143

Serotonin 5-HT2 receptor involvement in acute 5-HT-evoked scratching but not in allergic pruritus induced by dinitrofluorobenzene in rats.
Periodical: Journal of Pharmacology and Experimental Therapeutics Index Medicus:
Authors: Nojima H, Carstens E ART
Yr: 2003 Vol: 306 Nbr: 1 Abs: Pg: 245-252

c-fos expression in superficial dorsal horn of cervical spinal cord associated with spontaneous scratching in rats with dry skin.
Periodical: Neuroscience Letters Index Medicus:
Authors: Nojima H, Iodi Carstens M, Carstens E ART
Yr: 2003 Vol: 347 Nbr: Abs: Pg: 62-64

Opioid modulation of scratching and spinal c-fos expression evoked by intradermal serotonin.
Periodical: Journal of Neuroscience Index Medicus:
Authors: Nojima H, Simons CT, Cuellar JM, Iodi Carstens M, Carstens E ART
Yr: 2003 Vol: 23 Nbr: Abs: Pg: 10784-10790

Spinal c-fos expression associated with spontaneous biting in a mouse model of dry skin pruritus.
Periodical: Neuroscience Letters Index Medicus:
Authors: Nojima H, Cuellar JM, Simons CT, Iodi Carstens M, Carstens E ART
Yr: 2004 Vol: 361 Nbr: Abs: Pg: 79-82

It hurts so good: oral irritation by spices and carbonated drinks and the underlying neural mefhanisms (2002)
Periodical: Food Quality Preferences Index Medicus:
Authors: Carstens, E., Iodi Carstens, M., Dessirier, J. M, O'Mahony, M., Simons ART
Yr: 2002 Vol: 13 Nbr: 7-8 Abs: Pg: 431-443

Responses of superficial dorsal horn neurons to intradermal serotonin and other irritants comparison with scratching behavior (2002)
Periodical: Journal of Neurophysiology Index Medicus:
Authors: Jinks, S.L and Carstens E, ART
Yr: 2002 Vol: 87 Nbr: Abs: Pg: 1280-1289

Intracutaneous application of pruritic and algesic chemicals elicits simiar distribution of c-Fos immunopostive neurons in rat superficial dorsal horn (2002)
Periodical: Experimental Brain Research Index Medicus:
Authors: Jinks, S.L., Simons, C.T., Dessirier, J-M., Iodi Carstens, M., Antognini, J.F. and Carsten ART
Yr: 2002 Vol: 145 Nbr: 4 Abs: Pg: 261-269

Reduced aversion to oral capsaicin following neurotoxic destruction of superficial medullary neurons expressing NK receptors (2002)
Periodical: Brain Research Index Medicus:
Authors: Simons, C.T., Gogineri, A., Iodi Carsterns, M., Carstens, E. ART
Yr: 2002 Vol: 945 Nbr: 1 Abs: Pg: 139-143