The journal of pain : official journal of the American Pain Society
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Fresh empirical evidence supports the notion that fear of movement-related pain can be acquired through associative learning. In the context of these findings, 2 ideas are appealing, yet uninvestigated. The first is that merely the intention to perform a painful movement acts as a covert conditioned stimulus (CS) inducing defensive fear responses (ie, gaining excitatory properties following Pavlovian acquisition). The second idea is that after extinction, fear of movement-related pain can easily be reinstated after unexpected painful stimuli (ie, reinstatement). In a voluntary differential conditioning movement paradigm with movements as CSs and a painful electrocutaneous stimulus as the unconditioned stimulus (pain-US), 2 groups were included (Experimental/Control). One movement (CS+) was followed by the pain-US and another movement (CS-) was not during acquisition, while the CS+ was no longer reinforced during extinction. Next, the Experimental group received 2 reinstating pain-USs, whereas the Control group did not. The CS+ but not the CS- evoked fear of movement-related pain in self-reports and eye-blink startles. Intriguingly, the mere intention to perform the painful movement produced higher eye-blink startle responses than the intention to perform the nonpainful movement. We also demonstrated nondifferential reinstatement in the verbal fear ratings in the Experimental group only. ⋯ This study demonstrates that the mere intention to perform a painful movement prior to the actual painful movement itself can come to elicit conditioned fear responses. These results suggest that actual movement may not be necessary to elicit pain-related fear responses, maintaining chronic pain-related fear, avoidance, and disability.
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Morphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that central nervous system glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG glia. Here we test the hypothesis that morphine-induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of severe pain, the influence of persistent inflammatory pain was also assessed. Administration of morphine, in the absence of persistent inflammatory pain, resulted in the rapid development of morphine tolerance and was accompanied by a significant increase in vlPAG glial activation. In contrast, persistent inflammatory hyperalgesia, induced by intraplantar administration of complete Freund's adjuvant (CFA), significantly attenuated the development of morphine tolerance. No significant differences were noted in vlPAG glial cell activation for CFA-treated animals versus controls. These results indicate that vlPAG glia are modulated by a persistent pain state, and implicate vlPAG glial cells as possible regulators of morphine tolerance. ⋯ The development of morphine tolerance represents a significant impediment to its use in the management of chronic pain. We report that morphine tolerance is accompanied by increased glial cell activation within the vlPAG, and that the presence of a persistent pain state prevented vlPAG glial activation and attenuated morphine tolerance.
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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.