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From the Townsend Letter
November 2016

Sniffing Out Pain
Part 1: Olfaction's Complex Connections of Emotions, Memory, and Pain Perception
by Sarah A. LoBisco, ND
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After the autobiographic memory induction, a significant change in mood was observed. Specifically, positive feelings, such as comfort and happiness, significantly increased, and negative feelings, such as anxiety, significantly decreased. There was also a significant decrease in HR and an increase in SCL with the nostalgic odor. IL-2 levels decreased in the Proust condition but not in the control.
According to the authors, the increase in SCL could have resulted from the participants' increased attention to the nostalgic odor, relating to the amygdala's role in the autonomic nervous system. The researchers also theorized that the cytokine response could have resulted from initiation of the endocannabinoid system from experiencing a positive emotional response, or through memory-evoked stimulation of the cholinergic system which could have modulated inflammation.
The limitations to these conclusions include the short exposure time to the smell, potential gender differences, and a change in cytokine distribution that can result from memory evocation.73 However, the study provides evidence of how odors affect not only emotion but also physiology.
Another clinical trial tested physiological response to smell by seeking to determine if presentation of positive nostalgic odors could trigger respiration changes as compared with control scents.
The study consisted of 23 subjects (8 males, 15 females) who first took part in a pretest interview in order to determine if they had ever experienced odor-evoked memories. The subjects who reported affirmation of a memory induced by a specific perfume were then selected for the study. These participants were asked about the characteristics of the induced memory (i.e., vividness, pleasantness, emotional intensity, label of the perfume, and details of the specific memory). The subjects' response to the perfume evoking solely a pleasant personal memory was confirmed prior to the experimental condition.
Two control odors were used as comparison to "Proust condition." One was the smell of roses, β-phenyl ethyl alcohol (PEA), which was considered a pleasant smell. The other was chamomile, which was previously studied to be classified as a "normal scent" that would not evoke an emotional response. Minute ventilation, tidal volume, respiratory frequency, O2 consumption, and end-tidal CO2 concentrations were used to determine changes in respiratory function in response to the odors.
Each subject was exposed to all three odors (the "Proust condition" odor and the two control odors) while wearing a face-mask transducer that measured their respiratory responses to the olfactory stimuli. There was a 30 second air interval to prevent adaptation and to ensure baseline levels were returned to normal before the next smell was presented. The subjective determinations of the scent were divided into three categories: subjective scale of emotions, subjective scale of context of memory, and subjective reaction to odor. Trait anxiety, which is known to affect respiration, was measured as a potential confounding factor.
The study found that high anxiety subjects had an elevated level of arousal during retrieval of the memory and may have experienced the same arousal level as when the event actually happened. The use of 17 subjects' scale data of the scent was averaged and compiled in stimuli bar graphs and the results were reported as follows:

Findings showed that auto-biographical memory retrieval was associated with increasing tidal volume and decreasing respiratory frequency more than during presentation of control odors. Subjective feelings such as emotional arousal during retrieval of the memory, arousal level of the memory itself, or pleasantness and familiarity toward the odor evoked by autobiographical memory were more specific emotional responses compared with those related to control odors.74

Therefore, olfactory stimulants have powerful evidence for their effect on emotions, memory, and physiology. The interconnections between the olfactory system and the amygdala offer a clinical application for using odorants to induce the "Proust phenomenon." This could result in evoking positive autobiographical memories and calming physiological states in our patients' favor to modulate chronic pain.75-77
The Smell of Taste
A final mechanism to explore that may relate to the analgesic effect of smell is based on "secondary characteristics," which considers the associations that exist between taste and smell.78 In this viewpoint, the underlying mechanism of analgesia to a sweet smelling odors is induced through the opioid reward system connected to its association with sweet tastes.78,79
To test this theory, 94 undergraduate students (28 male, 66 female) were assigned to one of three groups which differed in the type of odor received during a painful cold pressor test (CPT). The groups consisted of either a sweet-smelling odor (caramel), an unpleasant odor (civet), or a pleasant, but not sweet-smelling odor (an aftershave lotion). Intensity for smell was kept consistent across conditions. The goal of the experiment was "to test for potential odor-induced mood effects on pain, and to distinguish between effects due to pleasantness from those due to a specific sweet smell."
The CPT consisted of subjects immersing their dominant hand and forearm in water at about 5 °C for up to 4 minutes on two occasions. Each occasion was 15 minutes apart with either the odor present or absent. The mean VAS ratings of odor were used following the CPT to determine mood responses to the smell. Data was excluded if the subjects' rating of pleasantness did not match the odor group they were assigned to.
According to the author, "These results clearly indicate that odor sweetness, rather than pleasantness alone, produced an increase in the duration that the subject keeps their arm exposed to noxious cold. Together with the lack of differences between the groups in ratings of pain intensity, these results probably reflect differences in pain tolerance rather than pain reduction per se."
The author thought that these results could be explained by evaluative conditioning (EC). EC involves the hedonic qualities transferred from one stimulus to another while not under conscious awareness or pairing. In contrast, classical conditioning (CC) operates on a neutral stimulus eliciting the same physiological process as a biological stimulus through repeated pairing, in which the two stimuli are obviously linked.78 (CC was used in the rodent experiments explained above).
Although this study offered an additional theory, some limitations were that it did not test for emotional associations to the pleasant scent or sweet smelling test, nor was baseline affect determined.
Bioindividuality in Odor Processing Experiences and Clinical Implications
Due to the complexity of aromas with potentially hundreds of molecules, humans tend to weave them into a conceptual whole. Specifically, the brain encodes odor stimuli and synthesizes them into a "unified perceptual experience."80 This has several implications for choosing aromas for clinical use.
As noted above, perceptions and environmental conditions associated with differing odors can vary from person to person. Also, the same smell could evoke a positive or neutral emotional response in one person and induce a traumatic stress response in another. Furthermore, internal physiology can also affect odor perception and response.
In 1971, the journal Science published an article describing how one's current internal state modulates perception of the senses, "A given stimulus can induce a pleasant or unpleasant sensation depending on the subject's internal state." Alliesthesia was the word proposed to describe this concept, and this review, which also included a few short experiments (n = 1), demonstrated this phenomenon in thermoregulation, taste, and olfaction.
In regard to the sense of smell, the scent of orange syrup was considered pleasant in the fasting state; however, after ingestion of a glucose load, the olfactory stimulus was deemed "unpleasant." According to the author, "The existence of alliesthesia implies the presence of internal signals modifying the conscious sensations aroused from peripheral receptors. It is therefore necessary to question the existence of sensations aroused by direct stimulation of central receptors, such as hypothalamic temperature detectors, osmoreceptors, and others."81
In other words, perception does not occur in isolation, but is intertwined into a diverse context of physiological conditions and also psychological states.81,82
Personality can also bias how emotional information is processed, such that people who are emotionally labile may be more reactive to unpleasant sensations. A double-blind study of 75 subjects tested how current emotional state, personality type (neuroticism, anxiety, and introversion), and emotional stimuli bias sensory perception of neutral (rubbing alcohol), pleasant (lemon/orange), and unpleasant (fecal) odors. Subjects were exposed to 12 emotionally counterbalanced video clips and reported on their feelings of happiness, sadness, negativity/hostility, or neutrality after the scenes.
During each viewing, they were told that the room would be filled with a smell at any time and to ring a bell with its detection. They were then to rate the experience of the smell following the clip. Researchers measured the amount of time to detect each odorant and the intensity attributed to the odor. Interestingly, the authors found a gender effect. Specifically, olfactory reaction and intensity were augmented by emotional state in men, but not women. Furthermore, women had a slower detection rate of neutral versus pleasant odorants. The authors also found that neurotic and anxious individuals were more biased toward affective odors than neutral ones.83
Several biases existed in the study, including the researchers' unintentionally skewing results to unpleasantness or pleasantness by their explanation of the experiment to the participants. They explicitly stated, "The smell will be perceptible to most people. You may or may not like the way it smells."83 Furthermore, rubbing alcohol may not be a neutral smell to those who had traumatic disinfectant memories. This baseline perceptual bias was not assessed in the subjects.
Still, the results suggest that it may be important to determine emotional lability, personality, and alliesthesia when selecting scents to modulate pain and other physiological effects. These studies outline the importance of considering perception, emotional state, and associations when introducing an aromatic into a treatment protocol.
Gender and Pain
As noted above with odor perception, gender can also be a factor in response to stimuli. It has also been implicated in how one processes pain during states of emotional stress. One review article concluded that gender was found to moderate pain experiences, with females having a lower pain threshold. There was also an association with sensory pain dependent on anxiety sensitivity. Specifically, "High anxiety sensitive females reported greater sensory pain than low anxiety sensitive females. No effect of anxiety sensitivity on sensory pain was found among males."84
These gender differences in pain sensation and experience have been reported in medical research and in epidemiology studies of certain pain disorders.84,85 For example, women have a disparate rate of autoimmunity and a different, favorable response to opioids. Other factors that may interact with gender to cause differentiation of pain sensation are status of the pain subject, time of pain reporting, dimension/nature of the pain, environment of pain, and how the pain is reported.84
Therefore, using subjective and autobiographical memories modulated by aroma could be very helpful in individualized pain perception. Furthermore, the calming effect of emotional oils, which will be discussed in part 2, could be particularly effective in female patients, due to their multimodal effects of calming neurological and physiological response patterns.
There are complex interactions of odors modulating psychological and physiological responses. Olfactory processing is associated with the limbic system and has an effect on memory, emotions, and physiology. Emotional effect of odors and their relationship to pain perception are neurologically connected by the amygdala. The amygdala is intricately involved in pain processing through its associated CRF receptors and its role in the stress response of the HPA axis. Furthermore, mood state and environmental conditions modulate differences in odor perception, processing, and physiological changes, including pain response. This should be considered when using odorants in clinical practice.
We have now reviewed how odor and aroma alone affect pain processing through emotions and memory and that this has implications in treatment for pain conditions. Specifically, pleasant aromatic associations may entice physiological relaxation responses and modify pain perception.
In part 2 of this series, I will look at how aromatic compounds, which contain secondary metabolites, can provide powerful biochemical, physiological, and psychological effects on pain more profoundly than odor alone.

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Notes .pdf

Sarah LoBisco, NDSarah LoBisco, ND, is a graduate of the University of Bridgeport's College of Naturopathic Medicine (UBCNM). She is licensed in Vermont as a naturopathic doctor and holds a bachelor of psychology degree from State University of New York at Geneseo. Dr. LoBisco is a speaker on integrative health, has several publications, and has earned her certification in functional medicine. Dr. LoBisco currently incorporates her training as a naturopathic doctor and functional medicine practitioner through writing, researching, private practice, and her independent contracting work for companies regarding supplements, nutraceuticals, essential oils, and medical foods. Dr. LoBisco also enjoys continuing to educate and empower her readers through her blogs and social media. Her recent blog can be found at

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