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(671)
S18
Abstracts
(668) Unilateral inactivation of the central nucleus of the amygdala reduces neuropathic pain
(670) Working memory load attenuates moderate pain, but not high pain, in healthy individuals
J Brightwell, B Taylor; Tulane University Health Sciences Center, New Orleans, LA The amygdala, most known for opioid-mediated pain inhibition, has recently been linked to descending pain facilitation. Specifically, the latero-capsular part of the central nucleus of the amygdala (CeA), the ‘nociceptive amygdala’, exhibits enhanced excitability and synaptic plasticity in an inflammatory model of persistent pain. To test the hypothesis that the CeA contributes to behavioral signs of neuropathic pain, we transected the tibial and common peroneal branches of the left sciatic nerve, thus sparing the sural branch (spared nerve injury model), and implanted bilateral guide cannulae above the CeA in male SpragueDawley rats. 14 d following nerve injury, 4% lidocaine, 2% bupivacaine or saline was bilaterally injected in the CeA, followed by tests for mechanical allodynia [using von Frey hairs and a machine mounted probe (Ugo Basile)], mechanical hyperalgesia (gentle plantar application of a diaper pin), and cold allodynia (plantar application of acetone). Compared to saline, lidocaine and bupivacaine robustly reduced allodynia and hyperalgesia at the paw ipsilateral to injury (p’s ⬍ .05), and did not affect responses at the contralateral paw (p’s ⬎ .05). Unilateral lidocaine administration to the right CeA produced similar results, while administration to the left CeA had no effect. Experiments are in progress to determine the effects of unilateral CeA inactivation following nerve injury of the right sciatic nerve. The present results support the hypothesis that the CeA or fibers of passage play a facilitatory role in the maintenance of chronic neuropathic pain.
D Muramoto, J Younger, T Ueno, M Kirschen, S Mackey; Stanford University School of Medicine, Palo Alto, CA In this project, we investigated the effect of working memory load on pain perception in healthy individuals. Previous research has suggested that distraction can significantly reduce the experience of pain. We hypothesized that the engagement of working memory processes would similarly reduce pain. Eight male and nine female participants received noxious thermal stimuli while performing a computer-based cognitive task. The task, repeated in four sessions of 36 trials each, involved three stages. In the encoding phase, participants were shown a rapid sequence of letters. The sequence was randomly selected to be no load (zero letters), low load (two letters), moderate load (four letters) or high load (six letters). In the working memory phase, participants were instructed to remember the displayed letters, so that they could later recall if a specific letter had been displayed. During this 6-second interval period, participants were administered a thermal stimulus with one of four randomly determined temperatures: baseline, low-intensity, moderate-intensity, and high-intensity. Participants then rated the pain on a visual analog scale. In the recall phase, participants were shown a letter and asked to indicate whether or not it was presented in the earlier sequence. Results demonstrated that a high working memory load reduced pain ratings to a moderately-intensive stimulus by 35% (t ⫽ 4.5, p ⬍ 0.001). No pain reductions were found in the low-intensity and high-intensity conditions. Working memory had no impact on lowintensity pain, likely because of a floor effect. Pain in the high-intensity condition was likely too great to be affected by a cognitive task. These results suggest that, in healthy individuals, attention-demanding tasks can reduce the experience of pain.
B16 - Psychophysics/Hyperalgesia
(671) Recreational MDMA use associated with enhanced temporal summation of pain
(669) Multifactorial predictors of experimental thermal pain C Starr, T Houle, R Coghill; Wake Forest University School of Medicine, Winston-Salem, NC Understanding factors that predict pain experienced by subjects provides a way to better comprehend neural mechanisms involved in pain modulation. Several studies describe predictors for clinical pain, but few have attempted to predict experimental pain ratings using psychological factors and individual differences in sensory thresholds. To investigate predictive factors for experimental thermal pain sensitivity and pain tolerance, twenty-one healthy volunteers were enrolled for the study. Thermal pain thresholds, thermal detection thresholds, intensity, and unpleasantness VAS (Visual Analog Scale) ratings to heat and cold stimuli applied to ventral forearm were assessed. Self-assessment of pain sensitivity, State-Trait Anxiety Inventory (STAI), CES-D (Center for Epidemiological Studies Depression Scale), and PANAS-X (Positive and Negative Affect Schedule – Expanded Form) were completed prior to quantitative sensory testing. Principal component factor analysis was used to reduce a 22 variable predictor set to 5 composite predictors: warm detection threshold, pain positivity (self-assessment of pain sensitivity and positive affect), inter-threshold range (the difference of heat and cold pain thresholds), cold detection threshold, and negative mood (negative affect, STAI, and CES-D). Prediction of pain ratings was then made by multiple linear regression. A model of five composite predictors successfully predicted cold pain sensitivity (r2 ⫽ 0.614, P ⬍ 0.008) and heat pain sensitivity (r2 ⫽ 0.537, P ⬍ 0.027). Individual variable predictors were also used separately. Suprathreshold heat pain stimuli ratings were neither significantly predicted by subjects’ self-assessment of pain sensitivity (r2 ⫽ 0.068, P ⬍ 0.252) nor heat pain threshold (r2 ⫽ 0.058, P ⬍ 0.291). Interestingly, cold pain threshold proved to be a good predictor for suprathreshold heat pain stimuli rating (r2 ⫽ 0.221, P ⬍ 0.0317). These results suggest a combination of psychological and quantitative sensory tests may provide powerful multifactorial predictive models for experimental pain with much improvement over individual predictive variables.
R Edwards, M Smith, T Kronfli, U McCann; Johns Hopkins, Baltimore, MD Recent evidence suggests that long-term use of 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) adversely affects brain serotonergic functioning. As serotonin is intimately involved in pain modulation, a potentially important area of investigation is MDMA’s effects on the experience of pain. Only one previous study has examined this issue, reporting decreased cold pain tolerance in regular MDMA users. The aim of the present study was to evaluate psychophysical responses to a variety of noxious thermal and pressure stimuli in MDMA users and controls. Twenty-seven regular MDMA users were compared to 27 ageand sex-matched controls with no history of MDMA use. The groups did not differ in heat or pressure pain thresholds, or in ratings of cold pain intensity. However, significant group differences emerged on measures of temporal summation of pain (p’s⬍ .05), an index of spinal sensitizability that is implicated in the pathophysiology of chronic pain conditions such as fibromyalgia. In the present study, MDMA users demonstrated enhanced summation relative to controls. Interestingly, within the MDMA-using group, individual differences in lifetime MDA use were unrelated to individual differences in responses to noxious stimuli; subjects with a relatively mild history of MDMA use demonstrated the same degree of exaggerated temporal summation as subjects with the highest lifetime MDMA usage. However, individual differences in painrelated anxiety were significantly associated with heat pain responses within the MDMA group; subjects with relatively higher levels of anxiety demonstrated elevated pain ratings and the largest degree of temporal summation. These findings suggest the possibility that exposure to MDMA may be associated with enhanced responsiveness to repetitive or sustained suprathreshold noxious stimulation, that the threshold for adverse affects of MDMA use on pain processing may be relatively low, and that affective processes (e.g., anxiety about pain) are likely to play a contributory role in MDMA’s effects.
Abstracts
(668) Unilateral inactivation of the central nucleus of the amygdala reduces neuropathic pain
(670) Working memory load attenuates moderate pain, but not high pain, in healthy individuals
J Brightwell, B Taylor; Tulane University Health Sciences Center, New Orleans, LA The amygdala, most known for opioid-mediated pain inhibition, has recently been linked to descending pain facilitation. Specifically, the latero-capsular part of the central nucleus of the amygdala (CeA), the ‘nociceptive amygdala’, exhibits enhanced excitability and synaptic plasticity in an inflammatory model of persistent pain. To test the hypothesis that the CeA contributes to behavioral signs of neuropathic pain, we transected the tibial and common peroneal branches of the left sciatic nerve, thus sparing the sural branch (spared nerve injury model), and implanted bilateral guide cannulae above the CeA in male SpragueDawley rats. 14 d following nerve injury, 4% lidocaine, 2% bupivacaine or saline was bilaterally injected in the CeA, followed by tests for mechanical allodynia [using von Frey hairs and a machine mounted probe (Ugo Basile)], mechanical hyperalgesia (gentle plantar application of a diaper pin), and cold allodynia (plantar application of acetone). Compared to saline, lidocaine and bupivacaine robustly reduced allodynia and hyperalgesia at the paw ipsilateral to injury (p’s ⬍ .05), and did not affect responses at the contralateral paw (p’s ⬎ .05). Unilateral lidocaine administration to the right CeA produced similar results, while administration to the left CeA had no effect. Experiments are in progress to determine the effects of unilateral CeA inactivation following nerve injury of the right sciatic nerve. The present results support the hypothesis that the CeA or fibers of passage play a facilitatory role in the maintenance of chronic neuropathic pain.
D Muramoto, J Younger, T Ueno, M Kirschen, S Mackey; Stanford University School of Medicine, Palo Alto, CA In this project, we investigated the effect of working memory load on pain perception in healthy individuals. Previous research has suggested that distraction can significantly reduce the experience of pain. We hypothesized that the engagement of working memory processes would similarly reduce pain. Eight male and nine female participants received noxious thermal stimuli while performing a computer-based cognitive task. The task, repeated in four sessions of 36 trials each, involved three stages. In the encoding phase, participants were shown a rapid sequence of letters. The sequence was randomly selected to be no load (zero letters), low load (two letters), moderate load (four letters) or high load (six letters). In the working memory phase, participants were instructed to remember the displayed letters, so that they could later recall if a specific letter had been displayed. During this 6-second interval period, participants were administered a thermal stimulus with one of four randomly determined temperatures: baseline, low-intensity, moderate-intensity, and high-intensity. Participants then rated the pain on a visual analog scale. In the recall phase, participants were shown a letter and asked to indicate whether or not it was presented in the earlier sequence. Results demonstrated that a high working memory load reduced pain ratings to a moderately-intensive stimulus by 35% (t ⫽ 4.5, p ⬍ 0.001). No pain reductions were found in the low-intensity and high-intensity conditions. Working memory had no impact on lowintensity pain, likely because of a floor effect. Pain in the high-intensity condition was likely too great to be affected by a cognitive task. These results suggest that, in healthy individuals, attention-demanding tasks can reduce the experience of pain.
B16 - Psychophysics/Hyperalgesia
(671) Recreational MDMA use associated with enhanced temporal summation of pain
(669) Multifactorial predictors of experimental thermal pain C Starr, T Houle, R Coghill; Wake Forest University School of Medicine, Winston-Salem, NC Understanding factors that predict pain experienced by subjects provides a way to better comprehend neural mechanisms involved in pain modulation. Several studies describe predictors for clinical pain, but few have attempted to predict experimental pain ratings using psychological factors and individual differences in sensory thresholds. To investigate predictive factors for experimental thermal pain sensitivity and pain tolerance, twenty-one healthy volunteers were enrolled for the study. Thermal pain thresholds, thermal detection thresholds, intensity, and unpleasantness VAS (Visual Analog Scale) ratings to heat and cold stimuli applied to ventral forearm were assessed. Self-assessment of pain sensitivity, State-Trait Anxiety Inventory (STAI), CES-D (Center for Epidemiological Studies Depression Scale), and PANAS-X (Positive and Negative Affect Schedule – Expanded Form) were completed prior to quantitative sensory testing. Principal component factor analysis was used to reduce a 22 variable predictor set to 5 composite predictors: warm detection threshold, pain positivity (self-assessment of pain sensitivity and positive affect), inter-threshold range (the difference of heat and cold pain thresholds), cold detection threshold, and negative mood (negative affect, STAI, and CES-D). Prediction of pain ratings was then made by multiple linear regression. A model of five composite predictors successfully predicted cold pain sensitivity (r2 ⫽ 0.614, P ⬍ 0.008) and heat pain sensitivity (r2 ⫽ 0.537, P ⬍ 0.027). Individual variable predictors were also used separately. Suprathreshold heat pain stimuli ratings were neither significantly predicted by subjects’ self-assessment of pain sensitivity (r2 ⫽ 0.068, P ⬍ 0.252) nor heat pain threshold (r2 ⫽ 0.058, P ⬍ 0.291). Interestingly, cold pain threshold proved to be a good predictor for suprathreshold heat pain stimuli rating (r2 ⫽ 0.221, P ⬍ 0.0317). These results suggest a combination of psychological and quantitative sensory tests may provide powerful multifactorial predictive models for experimental pain with much improvement over individual predictive variables.
R Edwards, M Smith, T Kronfli, U McCann; Johns Hopkins, Baltimore, MD Recent evidence suggests that long-term use of 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) adversely affects brain serotonergic functioning. As serotonin is intimately involved in pain modulation, a potentially important area of investigation is MDMA’s effects on the experience of pain. Only one previous study has examined this issue, reporting decreased cold pain tolerance in regular MDMA users. The aim of the present study was to evaluate psychophysical responses to a variety of noxious thermal and pressure stimuli in MDMA users and controls. Twenty-seven regular MDMA users were compared to 27 ageand sex-matched controls with no history of MDMA use. The groups did not differ in heat or pressure pain thresholds, or in ratings of cold pain intensity. However, significant group differences emerged on measures of temporal summation of pain (p’s⬍ .05), an index of spinal sensitizability that is implicated in the pathophysiology of chronic pain conditions such as fibromyalgia. In the present study, MDMA users demonstrated enhanced summation relative to controls. Interestingly, within the MDMA-using group, individual differences in lifetime MDA use were unrelated to individual differences in responses to noxious stimuli; subjects with a relatively mild history of MDMA use demonstrated the same degree of exaggerated temporal summation as subjects with the highest lifetime MDMA usage. However, individual differences in painrelated anxiety were significantly associated with heat pain responses within the MDMA group; subjects with relatively higher levels of anxiety demonstrated elevated pain ratings and the largest degree of temporal summation. These findings suggest the possibility that exposure to MDMA may be associated with enhanced responsiveness to repetitive or sustained suprathreshold noxious stimulation, that the threshold for adverse affects of MDMA use on pain processing may be relatively low, and that affective processes (e.g., anxiety about pain) are likely to play a contributory role in MDMA’s effects.