The journal of pain : official journal of the American Pain Society
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The goal in the current study was to examine the analgesic effects of a pinch grip-force production task and a working memory task when pain-eliciting thermal stimulation was delivered simultaneously to the left or right hand during task performance. Control conditions for visual distraction and thermal stimulation were included, and force performance measures and working memory performance measures were collected and analyzed. Our experiments revealed 3 novel findings. First, we showed that accurate isometric force contractions elicit an analgesic effect when pain-eliciting thermal stimulation was delivered during task performance. Second, the magnitude of the analgesic effect was not different when the pain-eliciting stimulus was delivered to the left or right hand during the force task or the working memory task. Third, we found no correlation between analgesia scores during the force task and the working memory task. Our findings have clinical implications for rehabilitation settings because they suggest that acute force production by one limb influences pain perception that is simultaneously experienced in another limb. From a theoretical perspective, we interpret our findings on force and memory driven analgesia in the context of a centralized pain inhibitory response. ⋯ This article shows that force production and working memory have analgesic effects irrespective of which side of the body pain is experienced on. Analgesia scores were not correlated, however, suggesting that some individuals experience more pain relief from a force task as compared to a working memory task and vice versa.
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The activation of the adenosine monophosphate (AMP)-activated kinase (AMPK) has been associated with beneficial effects such as improvement of hyperglycemic states in diabetes as well as reduction of obesity and inflammatory processes. Recent studies provide evidence for a further role of AMPK in models of acute and neuropathic pain. In this study, we investigated the impact of AMPK on inflammatory nociception. Using 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin as AMPK activators, we observed anti-inflammatory and antinociceptive effects in 2 models of inflammatory nociception. The effects were similar to those observed with the standard analgesic ibuprofen. The mechanism appears to be based on regulation of the AMPKα2 subunit of the kinase because AMPKα2 knockout mice showed increased nociceptive responses that could not be reversed by the AMPK activators. On the molecular level, antinociceptive effects are at least partially mediated by reduced activation of different MAP-kinases in the spinal cord and a subsequent decrease in pain-relevant induction of c-fos, which constitutes a reliable marker of elevated activity in spinal cord neurons following peripheral noxious stimulation. In summary, our results indicate that activation of AMPKα2 might represent a novel therapeutic option for the treatment of inflammation-associated pain, providing analgesia with fewer unwanted side effects. ⋯ AMPK activation is associated with beneficial effects on diabetes and obesity. In addition, we have shown analgesic properties of pharmacologic AMPK activation in inflammatory nociception, indicating that AMPK might serve as a novel therapeutic target in pain with fewer unwanted side effects.
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Primary headaches such as migraine are postulated to involve the activation of sensory trigeminal pain neurons that innervate intracranial blood vessels and the dura mater. It is suggested that local activation of these sensory nerves may involve dural mast cells as one factor in local inflammation, causing sensitization of meningeal nociceptors. Immunofluorescence was used to study the detailed distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in whole-mount rat dura mater and in human dural vessels. The relative distributions of CGRP, CLR, and RAMP1 were evaluated with respect to each other and in relationship to mast cells, myelin, substance P, neuronal nitric oxide synthase, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide. CGRP expression was found in thin unmyelinated fibers, whereas CLR and RAMP1 were expressed in thicker myelinated fibers coexpressed with an A-fiber marker. CLR and RAMP1 immunoreactivity colocalized with mast cell tryptase in rodent; however, expression of both receptor components was not observed in human mast cells. Immunoreactive substance P fibers coexpressed CGRP, although neuronal nitric oxide synthase and vasoactive intestinal peptide expression was very limited, and these fibers were distinct from the CGRP-positive fibers. Few pituitary adenylate cyclase-activating polypeptide immunoreactive fibers occurred and some colocalized with CGRP. ⋯ This study demonstrates the detailed distribution of CGRP and its receptor in the dura mater. These data suggest that CGRP is expressed in C-fibers and may act on A-fibers, rodent mast cells, and vascular smooth muscle cells that express the CGRP receptor. These sites represent potential pathophysiological targets of novel antimigraine agents such as the newly developed CGRP receptor antagonists.
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Review Meta Analysis
Primary motor cortex function in complex regional pain syndrome: a systematic review and meta-analysis.
Dysfunction in the central nervous system is thought to underlie the movement disorders that commonly occur in complex regional pain syndrome (CRPS), with much of the literature focusing on reorganization of the primary motor cortex (M1). Presumed changes in the M1 representation of the CRPS-affected body part have contributed to new CRPS treatments, which are increasingly being integrated in the clinic. We systematically investigated the evidence for altered M1 function in CRPS. We adhered to rigorous systematic review procedure in our search strategy, risk-of-bias appraisal, and data extraction. Eighteen studies comprising 14 unique data sets were included. The included studies used several neuroimaging techniques, whose outcomes we grouped into M1 cortical excitability, spatial representation, reactivity, and glucose metabolism, and conducted meta-analyses where possible. Risk of bias across studies was high, mainly due to missing data and unblinded assessment of outcomes. No definitive conclusions can be drawn regarding M1 spatial representation, reactivity, or glucose metabolism in CRPS. There is limited evidence for bilateral M1 disinhibition in CRPS of the upper limb. ⋯ Despite widely held assumptions of primary motor cortex dysfunction in complex regional pain syndrome, there is only evidence to support bilateral disinhibition, and there is high risk of bias across the literature.
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Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience, including reflexive hyperalgesia measures, sensory and affective dimensions of pain, and impact of pain on function and quality of life. In this review, we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes as well as the main behavioral tests for assessing pain in each model. ⋯ Understanding animal models and outcome measures in animals will assist in translating data from basic science to the clinic.