The journal of pain : official journal of the American Pain Society
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The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-β-hydroxylase antibody conjugated to saporin (DβH-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus. DβH-saporin treatment itself did not alter mechanical withdrawal threshold, but enhanced mechanical hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve ligation. In the spinal dorsal horn of spinal nerve ligation rats, DβH-saporin treatment increased choline acetyltransferase immunoreactivity as well as immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1] and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve growth factor content. DβH-saporin treatment did not, however, alter the fractional release of acetylcholine from terminals by dexmedetomidine after nerve injury. These results suggest that endogenous tone of noradrenergic fibers is not necessary for the plasticity of α2-adrenoceptor analgesia and glial activation after nerve injury, but might play an inhibitory role on glial activation. ⋯ This study demonstrates that endogenous noradrenaline modulates plasticity of glia and cholinergic neurons in the spinal cord after peripheral nerve injury and hence influences the pathophysiology of spinal cord changes associated with neuropathic pain.
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In this study, we aimed to evaluate the antinociceptive interaction between intrathecally administered amiloride and morphine or clonidine. Using rats chronically implanted with lumbar intrathecal catheters, we examined the ability of intrathecal amiloride, morphine, clonidine, and mixtures of amiloride-morphine and amiloride-clonidine to alter tail-flick latency. To characterize any interactions, isobolographic analysis was performed. The effects of pretreatment with intrathecally administered naloxone or yohimbine were tested. Intrathecal administration of amiloride (25-150 μg), morphine (.25-10 μg), or clonidine (.5-10 μg) alone produced significant dose-dependent antinociception in the tail-flick test. The median effective dose (ED(50)) values for intrathecally administered amiloride, morphine, and clonidine were 120.5 μg, 5.0 μg, and 4.4 μg, respectively. Isobolographic analysis exhibited a synergistic interaction after coadministration of amiloride-morphine and amiloride-clonidine. Intrathecal pretreatment with naloxone (10 μg) completely blocked the antinociceptive effects of morphine and the amiloride-morphine mixture. Intrathecal pretreatment with yohimbine (20 μg) completely blocked the antinociceptive effect of clonidine and antagonized the effect of the amiloride-clonidine mixture. There was no motor dysfunction or significant change in blood pressure or heart rate after the intrathecal administration of amiloride, amiloride-morphine, and amiloride-clonidine. The synergistic effect observed after the coadministration of amiloride and morphine or clonidine suggests a functional interaction among calcium channels, μ-receptors and α(2)-receptors at the spinal cord level of the nociceptive processing system. ⋯ Although intrathecal morphine and clonidine produces pronounced analgesia, antinociceptive doses of intrathecal morphine and clonidine produce several side effects, including hypotension, bradycardia, sedation, and tolerance. This article presents antinociceptive synergistic interaction between amiloride and morphine, amiloride, and clonidine on thermal nociceptive tests in the rat.
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For 2 weeks following surgery, 55 patients with preexisting chronic pain (CP) reported daily postoperative pain with movement and at rest. Of these, 30 CP patients used opioid pharmacotherapy for CP management and 25 did not. We modeled pain resolution in each patient using a linear fit so that each patient yielded 2 scores for each pain rating: 1) an intercept, or initial level of pain, immediately after surgery; and 2) a slope, or rate of pain resolution. The patients not using opioid pharmacotherapy had a mean pain with movement intercept of 5.4 and a slope of -.20, while the patients using opioid pharmacotherapy had a significantly higher mean intercept of 7.68 (P = .001) and a slope of -.21, sustaining higher pain levels over days. The opioid pharmacotherapy patients had the same rate of pain resolution as the other CP patients, and both groups resolved their pain more slowly than normal surgery patients. Preexisting CP may predispose a patient undergoing surgery to a slower rate of postoperative pain resolution. Chronic pain patients who use opioids share this predisposition but in addition, they are at risk for markedly higher postoperative pain across the entire pain resolution trajectory. ⋯ This is an observational rather than a randomized controlled study, and as such is less definitive. Nonetheless, these findings are consistent with those of animal studies showing that prolonged exposure to opioids can produce opioid-induced hyperalgesia. Patients with opioid pharmacotherapy for chronic pain who undergo surgery merit special attention for acute pain management.
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Comparative Study
Observational learning and pain-related fear: an experimental study with colored cold pressor tasks.
The primary aim of the current study was to experimentally test whether pain-related fear can be acquired through observational learning, whether extinction occurs after actual exposure to the aversive stimulus, and whether pain-related fear was associated with increased pain ratings. During an observation phase, female volunteers watched a video showing models performing cold pressor tasks (CPT), of which the color served as a conditioned stimulus (CS). In a differential fear conditioning paradigm, each of 2 colors were either paired with models' painful (CS+) or neutral (CS-) facial expressions. Exposure consisted of participants performing CPTs of both colors (10°C). Self-reported fear of pain and expected pain ratings were obtained after the observation period, while actual pain and avoidance measures were obtained during and after exposure. Results show that after observing another person performing the CPT associated with the painful faces, subjects report more fear of pain and expect more intense and unpleasant pain as compared with the CPT associated with the neutral faces. This effect of observational learning on pain-related fear persisted until after exposure. During and after exposure no stimulus-type effect for pain ratings was found. This study provides preliminary evidence for observational learning of pain-related fear in humans. ⋯ Fear of pain can be more disabling than pain itself, and is a risk factor for chronic pain. Knowledge about the acquisition of pain-related fear may help to develop novel pain management programs. This study is one of the first to demonstrate the effects of observational learning on pain-related fear.
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The present study investigated the effects of social threat to physical integrity on reported pain and facial pain expression. Predictions of a cognitive appraisal model and a communicative perspective on pain expression were compared. Participants (N = 67) received 5 electric pain stimuli administered by a confederate. They were led to believe that 5 pain stimuli were the minimum, a fixed amount, or the maximum number of pain stimuli allowed, thereby varying the social threat posed by the confederate. Reported pain and facial pain expression were recorded during the delivery of pain stimuli. Increased perceived social threat led to an increase of reported pain, specifically for high pain catastrophizing participants, while it led to a reduction of facial pain expression. This is the first study to demonstrate that a social threat manipulation has opposite effects on reported pain and facial expression, suggesting differences in adaptive function for both forms of pain expression. ⋯ This is the first demonstration showing an increase in verbal pain report and a decrease in nonverbal pain expression at the same time during social threat. This knowledge may contribute to improving pain assessment in different contexts.