Irritant and analgesic effects of nicotine
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: 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.