The journal of pain : official journal of the American Pain Society
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Pain is associated with stimulation of some behaviors (eg, withdrawal reflexes) but depression of many other behaviors (eg, feeding, locomotion, positively reinforced operant behavior). Drugs that block reuptake of serotonin, norepinephrine, and/or dopamine are widely used to treat depression, and they have also emerged as useful drugs for treatment of pain. This study compared effects of selective and mixed-action inhibitors of serotonin, norepinephrine, and/or dopamine reuptake in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of dilute acid served as a noxious stimulus to stimulate a writhing response or depress intracranial self-stimulation (ICSS) in Sprague Dawley rats. Selective reuptake inhibitors of serotonin (citalopram, clomipramine) and norepinephrine (nisoxetine, nortriptyline) and a mixed-action reuptake inhibitor of serotonin and norepinephrine (milnacipran) blocked acid-stimulated writhing but failed to block acid-induced depression of ICSS. Selective dopamine reuptake inhibitors (RTI-113 [3ß-(4-chlorophenyl)tropane-2ß-carboxylic acid phenyl ester hydrochloride], bupropion) and a triple reuptake inhibitor of dopamine, serotonin, and norepinephrine (RTI-112 [3ß-(3-methyl-4-chlorophenyl)tropane-2ß-carboxylic acid methyl ester hydrochloride]) blocked both acid-stimulated writhing and acid-induced depression of ICSS, although these drugs also produced an abuse-related facilitation of ICSS in the absence of the noxious stimulus. These results support further consideration of dopamine reuptake inhibitors as candidate analgesics, although abuse liability remains a concern. ⋯ Monoamine reuptake inhibitors are used to treat depression and some forms of pain. This study examined effects of monoamine reuptake inhibitors in a preclinical assay of pain-related behavioral depression. The results support further consideration of dopamine reuptake inhibitors as candidate analgesics under selected circumstances, although abuse liability remains a concern.
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Review Meta Analysis
Inserting needles into the body: a meta-analysis of brain activity associated with acupuncture needle stimulation.
Acupuncture is a therapeutic treatment that is defined as the insertion of needles into the body at specific points (ie, acupoints). Advances in functional neuroimaging have made it possible to study brain responses to acupuncture; however, previous studies have mainly concentrated on acupoint specificity. We wanted to focus on the functional brain responses that occur because of needle insertion into the body. An activation likelihood estimation meta-analysis was carried out to investigate common characteristics of brain responses to acupuncture needle stimulation compared to tactile stimulation. A total of 28 functional magnetic resonance imaging studies, which consisted of 51 acupuncture and 10 tactile stimulation experiments, were selected for the meta-analysis. Following acupuncture needle stimulation, activation in the sensorimotor cortical network, including the insula, thalamus, anterior cingulate cortex, and primary and secondary somatosensory cortices, and deactivation in the limbic-paralimbic neocortical network, including the medial prefrontal cortex, caudate, amygdala, posterior cingulate cortex, and parahippocampus, were detected and assessed. Following control tactile stimulation, weaker patterns of brain responses were detected in areas similar to those stated above. The activation and deactivation patterns following acupuncture stimulation suggest that the hemodynamic responses in the brain simultaneously reflect the sensory, cognitive, and affective dimensions of pain. ⋯ This article facilitates a better understanding of acupuncture needle stimulation and its effects on specific activity changes in different brain regions as well as its relationship to the multiple dimensions of pain. Future studies can build on this meta-analysis and will help to elucidate the clinically relevant therapeutic effects of acupuncture.
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The verbal numerical rating scale (vNRS-11) is one of the most widely used scales for assessing pediatric pain intensity. The literature shows that it is a valid instrument for assessing pain intensity in children above 8 years of age. The aim of this work was to study whether the vNRS-11 is also a valid instrument when it is used with Catalan-speaking children between 6 and 8 years old. A total of 126 schoolchildren (mean age, 6.87; SD, .68) were interviewed individually. Participants reported the maximum intensity of the most frequent pain they had experienced in the previous 3 months, and the intensity they would experience in 3 circumstances, using the vNRS-11 and other widely used scales: the Faces Pain Scale-Revised (FPS-R), the mechanical visual analog scale (VAS), and the colored analog scale (CAS). They rated their affective state in relation to the pain experience and reported their pain-related disability. Participants also indicated which of the 4 scales they preferred. The vNRS-11 showed a high convergent construct validity (r = .73-.86), adequate discriminant validity (z = 2.05-5.55), and adequate criterion-related validity (r = .45-.70). The vNRS-11 was the second most preferred scale. ⋯ This study contributes to the increasing literature that supports the use of the vNRS-11 to assess pain intensity in children. Specifically, it shows that it can be used in children as young as 6 years of age.
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We have shown previously that electrical stimulation of the motor cortex reduces spontaneous painlike behaviors in animals with spinal cord injury (SCI). Because SCI pain behaviors are associated with abnormal inhibition in the inhibitory nucleus zona incerta (ZI) and because inactivation of the ZI blocks motor cortex stimulation (MCS) effects, we hypothesized that the antinociceptive effects of MCS are due to enhanced inhibitory inputs from ZI to the posterior thalamus (Po)-an area heavily implicated in nociceptive processing. To test this hypothesis, we used a rodent model of SCI pain and performed in vivo extracellular electrophysiological recordings in single well-isolated neurons in anesthetized rats. We recorded spontaneous activity in ZI and Po from 48 rats before, during, and after MCS (50 μA, 50 Hz; 300-ms pulses). We found that MCS enhanced spontaneous activity in 35% of ZI neurons and suppressed spontaneous activity in 58% of Po neurons. The majority of MCS-enhanced ZI neurons (81%) were located in the ventrorateral subdivision of ZI-the area containing Po-projecting ZI neurons. In addition, we found that inactivation of ZI using muscimol (GABAA receptor agonist) blocked the effects of MCS in 73% of Po neurons. Although we cannot eliminate the possibility that muscimol spread to areas adjacent to ZI, these findings support our hypothesis and suggest that MCS produces antinociception by activating the incertothalamic pathway. ⋯ This article describes a novel brain circuit that can be manipulated, in rats, to produce antinociception. These results have the potential to significantly impact the standard of care currently in place for the treatment of patients with intractable pain.