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A heat-capsaicin model of pain: anticipation significantly alters the perception of pain reduction
Abstracts (198) Heat-induced thermal hyperalgesia and the capsaicinheat sensitization model K Martucci, R Coghill, M Yelle; Wake Forest University School of Medicine, Winston-Salem, NC The capsaicin-heat sensitization model has been demonstrated as an effective method of inducing experimental central sensitization in humans. However, capsaicin and heat do not act synergistically to produce the central sensitization. Also, no clear assessment of the combined effects of noxious heat stimuli and chemical stimuli such as capsaicin cream has been made, and even the presence of thermal hyperalgesia following capsaicin-heat sensitization remains ambiguous. In this study, we assessed heat-induced sensitization and compared it to capsaicin-heat sensitization, to delineate the separate and combined effects of repeated suprathreshold noxious heat stimuli and topical capsaicin cream (0.1%) in healthy volunteers. Preliminary analyses showed that mean post-stimulus visual analog scale (VAS) ratings for short duration noxious stimuli were higher in response to thermal stimuli applied after heat 1 placebo sensitization evidencing heat-induced thermal hyperalgesia. Surprisingly, on days that involved heat 1 capsaicin sensitization, the heat-induced thermal hyperalgesia was not potentiated, but rather appeared to be reduced by the application of capsaicin. Peak VAS ratings extracted from real-time ratings confirmed that the thermal hyperalgesia was attenuated by application of capsaicin. Maximum VAS ratings for long duration stimuli (30 s) were effectively decreased in both the primary and secondary regions of mechanical allodynia following combined heat and capsaicin treatment. Thus, repeated noxious heat stimuli alone (without capsaicin) may constitute a simplified human model of thermal and mechanical hyperalgesia.
Diagnosis, Assessment, and Reviews B10 Endogenous Pain Modulation (199) Withdrawn by authors
(200) Increasing working memory load attenuates pain in healthy volunteers but not in chronic low back pain patients M Tieu, R McCue, V Gandhi, S Mackey; Stanford University Medical Center, Palo Alto, CA Cognitive deficits and decreased ability to maintain high working memory loads have been well documented in chronic pain patients. The interplay between acute pain processing and working memory, and how that interaction may differ between chronic pain patients and healthy controls, are not as well defined. This study aims to characterize the modulatory effect of working memory- a system for temporary storage of information necessary for complex cognitive tasks-on pain processing and vice-versa. We hypothesize that in healthy controls, pain intensity will decrease the accuracy of performance on a working memory task and that increasing working memory loads will attenuate the pain perception of an acute, thermal stimulus. For chronic pain patients, we hypothesize that pain intensity will also decrease the accuracy of performance, but that increasing working memory load will no longer attenuate pain perception. During the task, participants were presented with a series of letters, experienced a thermal pain stimulus on their left, thenar eminence, and then rated their pain. They were then asked whether a specific letter was presented in the initial series of letters. The task contained four different working memory loads and four different pain stimuli that were determined from pre-task thresholding. For both the healthy controls and chronic back pain patients, the highest pain stimulus decreased accuracy on the working memory task at the highest difficulty level by 13%. For healthy controls, engagement of the working memory task resulted in a statistically significant 10% pain reduction at the highest pain stimulus (p = .02). Additionally, the amount of pain reduction and the overall performance on the highest difficulty level were strongly correlated: those who performed best at the task had the largest reduction in pain. For chronic pain patients, however, engagement of the working memory task did not attenuate pain perception (p = .67).
S25 (201) Cumulative effects of reward and loss on pain evaluation R McCue, J Lawrence, B Knutson, S Mackey; Stanford University Medical Center, Palo Alto, CA Recent research has shown that the engagement of reward systems can reduce pain. However, the modulation of acute pain by these systems is poorly understood. Using a task know to elicit reward systems, the Monetary Incentive Delay (MID) task, and a thermal noxious stimulus, we hypothesized that monetary rewards would lead to an overall reduction in self-reported pain. Each trial consisted of a cue indicating participants were playing to win $5 (positive risk), to avoid losing $5 (negative risk), or with no money at stake (neutral risk). Following a time-variable delay, the subject had to respond to a visual target before it disappeared to win the trial. The outcome of each trial and the cumulative earnings were displayed, which was followed by a heat stimulus of no, low, medium, or high intensity. Self-reported pain was then rated using a visual analogue scale. 13 healthy volunteers underwent 2 sessions of the MID task; in the ‘‘increasing’’ phase, the success rate of the game was fixed so that participants steadily gained money. In the ‘‘decreasing’’ phase, participants steadily lost money. Results indicated that with high thermal intensity, cumulative winnings are associated with an 11% reduction of pain, while cumulative losses led to a 4.2% increase in pain (p = .025). Also for high intensity heat, we found that trials where individuals lost $5 were rated as more painful than trials where they won $5 (p = .012). However, negative risk trials were rated as significantly more painful than positive and neutral risk trials (p < .001), and when risk was analyzed together with trial outcome, outcome was no longer significant (p = .71). Our findings indicate that the cumulative amount of money earned or lost, as well as the risk of a trial, significantly affect pain ratings, thereby supporting our hypothesis that reward systems modulate the pain experience.
(202) A heat-capsaicin model of pain: anticipation significantly alters the perception of pain reduction J Brown, H Ung, S Mackey; Stanford University, Stanford, CA The mechanisms of nociceptive processing have been extensively researched; however, the perception of pain reduction remains poorly understood. To investigate the relationship between decreases in noxious intensity and decreases in pain, we developed a model to deliver prolonged noxious heat while minimizing the risk of burn. Using a heat-capsaicin model of pain, we hypothesized that pain decreases monotonically with decreases in noxious intensity, and that anticipation significantly changes the perception of decreases in pain. 16 healthy volunteers participated in this experiment. 0.5 mL of 0.075% capsaicin cream was applied to the volar forearm and allowed to sit for 30 minutes before removal. A Medoc TSA-II thermal sensory analyzer was placed at the site of capsaicin application. Each subject underwent multiple trials, each trial consisting of 12 seconds of heat, after which the thermode was 1) maintained at a constant temperature for an additional twenty-four seconds, 2) cooled to a lower, but still noxious temperature for an additional twenty-four seconds, or 3) returned to baseline. Drops in temperature were either preceded by a cue or were uncued. Throughout the experimental procedure, participants provided continuous self-report of perceived pain. On a scale from 0-10, all participants reported pain intensity equal to 7 at or below 44C. Participants reported significant reduction in pain following a 1C decrease in temperature (p < 0.001), and compared to a 1C decrease there was significantly greater reduction in pain when temperature was returned to baseline (p < 0.001). In addition, a 35% greater reduction in pain was perceived when a 1C decrease was anticipated compared to when it was not anticipated (p < 0.05). We have developed a model where capsaicin and innocuous heating are used to safely study pain reduction. Our findings demonstrate that anticipation significantly alters the perception of reduced pain. (This work is supported by NINDS RO1 NS053961.)
Diagnosis, Assessment, and Reviews B10 Endogenous Pain Modulation (199) Withdrawn by authors
(200) Increasing working memory load attenuates pain in healthy volunteers but not in chronic low back pain patients M Tieu, R McCue, V Gandhi, S Mackey; Stanford University Medical Center, Palo Alto, CA Cognitive deficits and decreased ability to maintain high working memory loads have been well documented in chronic pain patients. The interplay between acute pain processing and working memory, and how that interaction may differ between chronic pain patients and healthy controls, are not as well defined. This study aims to characterize the modulatory effect of working memory- a system for temporary storage of information necessary for complex cognitive tasks-on pain processing and vice-versa. We hypothesize that in healthy controls, pain intensity will decrease the accuracy of performance on a working memory task and that increasing working memory loads will attenuate the pain perception of an acute, thermal stimulus. For chronic pain patients, we hypothesize that pain intensity will also decrease the accuracy of performance, but that increasing working memory load will no longer attenuate pain perception. During the task, participants were presented with a series of letters, experienced a thermal pain stimulus on their left, thenar eminence, and then rated their pain. They were then asked whether a specific letter was presented in the initial series of letters. The task contained four different working memory loads and four different pain stimuli that were determined from pre-task thresholding. For both the healthy controls and chronic back pain patients, the highest pain stimulus decreased accuracy on the working memory task at the highest difficulty level by 13%. For healthy controls, engagement of the working memory task resulted in a statistically significant 10% pain reduction at the highest pain stimulus (p = .02). Additionally, the amount of pain reduction and the overall performance on the highest difficulty level were strongly correlated: those who performed best at the task had the largest reduction in pain. For chronic pain patients, however, engagement of the working memory task did not attenuate pain perception (p = .67).
S25 (201) Cumulative effects of reward and loss on pain evaluation R McCue, J Lawrence, B Knutson, S Mackey; Stanford University Medical Center, Palo Alto, CA Recent research has shown that the engagement of reward systems can reduce pain. However, the modulation of acute pain by these systems is poorly understood. Using a task know to elicit reward systems, the Monetary Incentive Delay (MID) task, and a thermal noxious stimulus, we hypothesized that monetary rewards would lead to an overall reduction in self-reported pain. Each trial consisted of a cue indicating participants were playing to win $5 (positive risk), to avoid losing $5 (negative risk), or with no money at stake (neutral risk). Following a time-variable delay, the subject had to respond to a visual target before it disappeared to win the trial. The outcome of each trial and the cumulative earnings were displayed, which was followed by a heat stimulus of no, low, medium, or high intensity. Self-reported pain was then rated using a visual analogue scale. 13 healthy volunteers underwent 2 sessions of the MID task; in the ‘‘increasing’’ phase, the success rate of the game was fixed so that participants steadily gained money. In the ‘‘decreasing’’ phase, participants steadily lost money. Results indicated that with high thermal intensity, cumulative winnings are associated with an 11% reduction of pain, while cumulative losses led to a 4.2% increase in pain (p = .025). Also for high intensity heat, we found that trials where individuals lost $5 were rated as more painful than trials where they won $5 (p = .012). However, negative risk trials were rated as significantly more painful than positive and neutral risk trials (p < .001), and when risk was analyzed together with trial outcome, outcome was no longer significant (p = .71). Our findings indicate that the cumulative amount of money earned or lost, as well as the risk of a trial, significantly affect pain ratings, thereby supporting our hypothesis that reward systems modulate the pain experience.
(202) A heat-capsaicin model of pain: anticipation significantly alters the perception of pain reduction J Brown, H Ung, S Mackey; Stanford University, Stanford, CA The mechanisms of nociceptive processing have been extensively researched; however, the perception of pain reduction remains poorly understood. To investigate the relationship between decreases in noxious intensity and decreases in pain, we developed a model to deliver prolonged noxious heat while minimizing the risk of burn. Using a heat-capsaicin model of pain, we hypothesized that pain decreases monotonically with decreases in noxious intensity, and that anticipation significantly changes the perception of decreases in pain. 16 healthy volunteers participated in this experiment. 0.5 mL of 0.075% capsaicin cream was applied to the volar forearm and allowed to sit for 30 minutes before removal. A Medoc TSA-II thermal sensory analyzer was placed at the site of capsaicin application. Each subject underwent multiple trials, each trial consisting of 12 seconds of heat, after which the thermode was 1) maintained at a constant temperature for an additional twenty-four seconds, 2) cooled to a lower, but still noxious temperature for an additional twenty-four seconds, or 3) returned to baseline. Drops in temperature were either preceded by a cue or were uncued. Throughout the experimental procedure, participants provided continuous self-report of perceived pain. On a scale from 0-10, all participants reported pain intensity equal to 7 at or below 44C. Participants reported significant reduction in pain following a 1C decrease in temperature (p < 0.001), and compared to a 1C decrease there was significantly greater reduction in pain when temperature was returned to baseline (p < 0.001). In addition, a 35% greater reduction in pain was perceived when a 1C decrease was anticipated compared to when it was not anticipated (p < 0.05). We have developed a model where capsaicin and innocuous heating are used to safely study pain reduction. Our findings demonstrate that anticipation significantly alters the perception of reduced pain. (This work is supported by NINDS RO1 NS053961.)