Irritant and pain-reducing 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: It is well-known that tobacco smoke irritates the eyes, nose and mouth. This irritation is due to nicotine, an active chemical in tobacco. Nicotine also reduces the sensation of pain, and it has been suggested that smokers become addicted to nicotine because of its pain-reducing and calming effects, and that they avoid quitting because of the increased pain and discomfort that occurs during withdrawal. This proposal will study both the irritating and the pain-reducing effects of nicotine, and how these effects might be signaled by the brain. The primary goals of this project are (1) to better understand the biology of nicotine irritation, (2) to better understand biologically how nicotine reduces pain, and (3) to use modern research methods to determine if young smokers have less pain, and if they experience more pain when they quit smoking. A scientific understanding of the irritating effect of nicotine is important in objectively developing policies on exposure to second-hand smoke. It will also clarify the role that the sensory impact or "kick" of cigarette smoke has in nicotine addiction, which might be similar to the preference that many people have for spicy foods. An improved understanding of the pain-reducing effect of nicotine is directly relevant to understanding nicotine addiction, and the role that pain and discomfort play in efforts to quit smoking.
 
 
 
 
 
 In one experiment, participants will have a weak solution of nicotine placed onto their tongue and will rate how irritating it is. Since we want to know how nicotine irritates the tongue, we will place different chemicals onto the tongue that are known to block nicotine "receptors" (proteins that recognize nicotine in a "lock and key" manner to cause irritation). Nicotine will then be placed onto the same area of the tongue receiving the blocker, and participants rate how irritating it is. We predict that certain blockers will reduce the irritation caused by nicotine. We will also test if menthol, a chemical in mentholated cigarettes that causes a cool sensation, reduces irritation caused by nicotine. In animals, we will record the electrical activity of single nerve cells in the brain that are involved in signaling irritation of the tongue or eye in. We want to determine if individual nerve cells signal irritation by only one chemical such as nicotine, or if they respond indiscriminately to various types of irritating chemicals such as salt, acid, or capsaicin (the chemical in red peppers that causes a burning sensation). The answer to this question is important in understanding how the brain is able to tell the difference between irritating substances, and our results so far indicate that nerve cells are activated by both nicotine and many other chemicals. We also want to study the receptors for nicotine that cause this activation. Similar experiments will also be done to determine if the transmission of pain signals are blocked when nicotine is administered into certain areas of the brain containing nicotine receptors. We are also interested in testing if nicotine has less of a pain-reducing effect in animals that are continually exposed to nicotine for a long period of time (like chronic smokers), and if pain signals increase during withdrawal from nicotine.
 
 
 
 
 
 Another project will test the hypothesis that young adult chronic smokers are less sensitive to experimental pain than non-smokers because of the pain-reducing effect of nicotine, and that chronic smokers will have increased pain sensitivity during voluntary withdrawal from smoking. This hypothesis will be tested in groups of young smokers and non-smokers matched according to age, gender and ethnicity. The participants will rate the intensity of heat pain on the skin, and whether they can detect small temperature changes. We predict that the smokers will give lower pain ratings and will not be able to detect small temperature changes as well as non smokers because of the pain-reducing effect of nicotine.