Greater Conditioned Pain Modulation Research Articles

Greater Conditioned Pain Modulation Is Associated With Enhanced Morphine Analgesia in Healthy Individuals and Patients With Chronic Low Back Pain.

Conditioned pain modulation (CPM) protocols index magnitude of descending pain inhibition. This study evaluated whether the degree of CPM, controlling for CPM expectancy confounds, was associated with analgesic and subjective responses to morphine and whether chronic pain status or sex moderated these effects. Participants included 92 individuals with chronic low back pain and 99 healthy controls, none using daily opioid analgesics. In a cross-over design, participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo before undergoing evoked pain assessment. In each session, participants engaged in ischemic forearm and heat pain tasks, and a CPM protocol combining ischemic pain (conditioning stimulus) and heat pain (test stimulus). Placebo-controlled morphine outcomes were derived as differences in pain and subjective effects across drug conditions. In hierarchical regressions controlling for CPM expectancies, greater placebo-condition CPM was associated with less subjective morphine unpleasantness (P=0.001) and greater morphine analgesia (P's<0.05) on both the ischemic pain task (Visual Analog Scale Pain Intensity and Unpleasantness) and heat pain task (Visual Analog Scale Pain Intensity, McGill Pain Questionnaire-Sensory, and Present Pain Intensity subscales). There was no moderation by sex or chronic low back pain status, except for the ischemic Present Pain Intensity outcome for which a significant 2-way interaction (P<0.05) was noted, with men showing a stronger positive relationship between CPM and morphine analgesia than women. Results suggest that CPM might predict analgesic and subjective responses to opioid administration. Further evaluation of CPM as an element of precision pain medicine algorithms may be warranted.

Dissociation of Endogenous Pain Inhibition Due to Conditioned Pain Modulation and Placebo in Male Athletes Versus Nonathletes.

Animals and humans are able to inhibit pain by activating their endogenous pain-inhibition system. Endurance athletes possess a higher pain-tolerance threshold and a greater conditioned pain modulation (CPM) effect than nonathletes, suggesting better endogenous pain inhibition. In addition to CPM, placebo is another prominent paradigm used to test endogenous pain inhibition. However, whether the placebo effect and the CPM effect share the same mechanisms of pain inhibition has not been investigated. If there is a shared mechanism, then endurance athletes should show not only a better CPM effect than nonathletes but also a greater placebo effect. Here, we investigated 16 male endurance athletes and 17 male nonathletes in well-established placebo and CPM paradigms to assess whether endurance athletes have a better endogenous pain-inhibition system than nonathletes. As expected, we find a significantly greater CPM effect in athletes than in nonathletes. In contrast, we could only find a significant placebo effect in nonathletes. Explorative analyses reveal negative associations between the placebo effect and heart rate variability as well as between the placebo effect and interoceptive awareness. Together, the results demonstrate a dissociation of endogenous pain inhibition of CPM and placebo effect between endurance athletes and nonathletes. This suggests that both effects are based, at least in part, on different biological mechanisms.

Conditioned pain modulation predicts exercise-induced hypoalgesia in healthy adults.

Conditioned pain modulation (CPM) is the concept that pain inhibits pain and has potential rehabilitation implications for exercise prescription. The purpose of this study was to determine whether changes in pressure pain perception after a thermal conditioning stimulus (i.e., CPM) was attenuated with aging and whether CPM predicted pain relief after exercise (exercise-induced hypoalgesia (EIH)) in healthy young and older adults. Twenty young (21.9 ± 3.3 yr, 10 men) and 19 older (72.0 ± 4.5 yr, 10 men) adults participated in three sessions: one familiarization and two experimental (EIH and CPM) sessions. Pressure pain perception was assessed using a weighted Lucite edge placed on the right index finger for 1 min. EIH was determined by measuring pressure pain perception before and after prolonged submaximal isometric contraction of the elbow flexors. CPM was assessed by measuring pressure pain perception at the finger while the foot was immersed in neutral water versus painful ice water. Young, but not older, adults reported a decrease in pressure pain at the finger while their foot was immersed in the ice water bath compared with the neutral bath (i.e., CPM, trial-age: P = 0.001). Pressure pain ratings decreased after exercise (P = 0.03) that was perceived as painful (peak arm pain, 7.0 ± 3.3) for both young and older adults. Regression analysis showed that after controlling for age and baseline pain, CPM predicted EIH (model adjusted R = 0.23, P = 0.007). CPM was attenuated in older adults, as measured with a noxious pressure stimulus after a thermal conditioning stimulus, and adults with greater CPM were more likely to report greater EIH.

Self-reported Physical Activity Predicts Pain Inhibitory and Facilitatory Function

Considerable evidence suggests regular physical activity can reduce chronic pain symptoms. The dysfunction of endogenous facilitatory and inhibitory systems has been implicated in multiple chronic pain conditions. However, few studies have investigated the relationship between levels of physical activity and descending pain modulatory function. The purpose of this study was to determine whether self-reported levels of physical activity in healthy adults predicted 1) pain sensitivity to heat and cold stimuli, 2) pain facilitatory function as tested by temporal summation (TS) of pain, and 3) pain inhibitory function as tested by conditioned pain modulation (CPM) and offset analgesia. Forty-eight healthy adults (age range = 18-76 yr) completed the International Physical Activity Questionnaire (IPAQ) and the following pain tests: heat pain thresholds, heat pain suprathresholds, cold pressor pain, TS of heat pain, CPM, and offset analgesia. The IPAQ measured levels of walking, moderate, vigorous, and total physical activity over the past 7 d. Hierarchical linear regressions were conducted to determine the relationship between each pain test and self-reported levels of physical activity while controlling for age, sex, and psychological variables. Self-reported total and vigorous physical activity predicted TS and CPM (P < 0.05). Individuals who self-reported more vigorous and total physical activity exhibited reduced TS of pain and greater CPM. The IPAQ measures did not predict any of the other pain measures. These results suggest that healthy older and younger adults who self-report greater levels of vigorous and total physical activity exhibit enhanced descending pain modulatory function. Improved descending pain modulation may be a mechanism through which exercise reduces or prevents chronic pain symptoms.

The association of elevated resting blood pressure with greater conditioned pain modulation is present for men but not women

Elevated resting blood pressure (BP) is consistently associated with hypoalgesia (i.e., diminished pain responsiveness) in healthy normotensive individuals. It has been suggested that sex might moderate BP-related hypoalgesia, such that BP-related hypoalgesia may be stronger in men compared to women. At this time it remains unclear whether resting BP is also associated with conditioned pain modulation (CPM), an endogenous, opioid-mediated pain inhibitory process that is often mechanistically associated with hypoalgesia.