Human neurophysiology of nicotine analgesia: sex differences
Initial Award Abstract
Nicotine addiction is a powerful process that is not well understood. The ability of nicotine to reduce pain and discomfort has been proposed as a mechanism underlying smoking addiction. The majority of human studies have found pain-reducing effects, while others, especially those using women subjects, have not. Furthermore, a recent study found that nicotine reduced pain for men, but not women. These findings suggest an important gender difference in the mechanisms of smoking that lead to addiction.
We will use state-of-the-art techniques for assessing pain and pain-reduction to test for the reality and magnitude of nicotine's pain-reducing effects in both smokers and nonsmokers; their possible dependence on gender; and their possible dependence on menstrual cycle phase in women. These techniques will include the use of an objective, neurophysiological measure of pain. Measures of the electrical activity of the brain that can be recorded with electrodes placed on the head have been shown to be sensitive to a number of different pain-reducing treatments. We have developed a measure that can differentiate pain from other, non-pain aspects of sensory processing. In addition, we will assess pain-reduction from nicotine with three other pain measures: the amount of painful electrical current needed to produce a just painful sensation; the amount of heat needed to produce a just painful sensation; and subject's ratings of the painfulness of electrical pulses across a range of pain intensities.
Nicotine will be administered using a computer controlled intravenous infusion to produce and maintain stable target blood levels of nicotine. This will allow us to exert precise control over nicotine levels in both smokers and nonsmokers. In contrast to other methods of providing nicotine that involve multiple, small amounts of drug and rapidly changing blood levels (smoking, nasal spray) or more slowly changing blood levels (skin patch, gum), computer controlled infusions will provide the stable blood concentrations necessary for the approximately 45 minute set of tests of pain-reduction.
Each subject will participate in two infusion sessions: one for nicotine and one for a non-active substance. Each session will include two sets of pain measures: a pre-drug baseline set and a drug infusion set. Procedures will be identical in each set.
Specifically, we hypothesize that, using a procedure where neither the subject nor the technician running the session knows whether the drug given is nicotine or a non-active substance, intravenous nicotine will provide more pain reduction for men than for women. We will test this hypothesis separately in groups of 60 smokers and 60 nonsmokers. Furthermore, we will relate the degree of pain-reduction produced in each smoking subject to his or her own patterns of smoking behavior (using the Smoking Occasions Questionnaire) in order to evaluate whether the pain-reduction effect is associated with the use of smoking to relieve physical and emotional discomfort. In a second study, 20 women subjects will participate in nicotine sessions during each of three different phases of the menstrual cycle. We hypothesize that the pain-reducing effects of nicotine will vary across the menstrual cycle. |