The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Pain relief is associated with improvement in motor function in complex regional pain syndrome type 1: secondary analysis of a placebo-controlled study on the effects of ketamine.
There are indications of motor circuit changes in patients with complex regional pain syndrome (CRPS). Nevertheless, although several studies have analyzed motor behavior in CRPS, a relation with pain could not be detected. This might be explained by the use of cross-sectional designs in these studies, in which pain is considered as a trait- rather than a state-dependent variable. We therefore studied the time-dependent relation between pain and motor function in affected arms of 29 CRPS patients during their participation in a placebo-controlled ketamine study. Movement parameters (velocity, frequency, amplitude, and number of arrests) were assessed during a finger tapping task. Linear mixed model analysis of the effects of pain (numerical rating scale score), treatment (ketamine/placebo), and week (1, 3, 6, and 12 weeks after treatment) on the movement parameters revealed that pain intensity was significantly (inversely) related to motor function, irrespective of whether patients had received ketamine or placebo. Movement parameters changed 3-12% per point numerical rating scale change. Because patients were unaware of possible effects of ketamine on motor function, these findings suggest that motor function changes were mediated by, or occurred simultaneously with, changes in pain intensity. By improving motor function, pain relief may offer a window of opportunity for rehabilitation programs in CRPS. ⋯ This article provides evidence for a direct relation between pain and motor function in CRPS, which indicates that pain relief may be an important factor in the treatment of motor disturbances in this condition. These findings may help to advance our understanding of the pathways underlying motor disturbances in CRPS.
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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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Studies of peripheral nerve inflammation (neuritis) suggest that some symptoms of neuropathic pain can be generated from inflamed but otherwise uninjured axons. We have previously inferred a role for inflammation-induced axonal transport disruption in the underlying mechanisms. In the present study, we have investigated the development of sensory hypersensitivities following vinblastine-induced axonal transport disruption. Similar to neuritis, locally applied .1 mM vinblastine caused the rapid development of mechanical hypersensitivity within the first week postsurgery. The same animals did not develop heat hypersensitivity. Because aberrant firing from primary sensory neurons is considered necessary to drive spinal mechanisms that lead to hypersensitivities, the levels of ongoing activity and axonal mechanical sensitivity were examined. Recordings from A- and C-fiber neurons did not reveal differences in the levels of ongoing activity between vinblastine-treated (<5.8%) and saline-treated control animals (<4.6%). However, 28% of C-fiber axons were mechanically sensitive at the vinblastine treatment site. Using kinesin immunohistochemistry, we confirmed a reduction of anterograde axonal transport in vinblastine-treated and neuritis animals. In summary, this study has revealed an alternative pain model, which may be relevant to conditions that are not accompanied by frank nerve injury. ⋯ In this study, we expand our previous reports and demonstrate that focal reduced axonal transport causes distal mechanical hypersensitivity considered consistent with neuropathic pain but in the absence of nerve injury. These findings may inform pain conditions that have a neural inflammatory component.
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Somatic symptoms experienced by women with a menstrually related mood disorder (MRMD) during their premenstrual luteal phase contribute to functional impairment. Yet, investigations on pathophysiological mechanisms contributing to heightened pain sensitivity in MRMD are sparse. During the luteal phase, 61 women with an MRMD and 61 non-MRMD controls were evaluated for β-adrenergic receptor (β-AR) responsivity using the isoproterenol sensitivity test. A subset (43 MRMD and 50 non-MRMD) then entered a double-blind, placebo-controlled, crossover protocol to examine the effect of β-AR blockade with intravenous propranolol on sensitivity to experimental (cold pressor and ischemic) and clinical (McGill Pain Questionnaire score) pain. Women with an MRMD exhibited greater β1- and β2-AR responsivity, ischemic pain intensity, and affective clinical pain ratings than controls. Propranolol increased cold pressor pain tolerance in both groups, but it decreased cold pain intensity and ischemic pain unpleasantness ratings only in non-MRMD women. In contrast, propranolol decreased affective ratings of clinical pain in women with MRMD. Exploratory analyses indicated that only in MRMD women did greater β-AR responsivity predict greater sensitivity to cold pressor and ischemic pain. This study provides the first evidence for a role of β-AR mechanisms in the hyperalgesia and clinical pain experienced by women with MRMDs. ⋯ This article describes the effects of β-adrenergic receptor stimulation and blockade on experimental and clinical pain sensitivity in women with an MRMD. The results of this study may have implications for the management of the substantial somatic premenstrual symptomatology experienced by women with an MRMD.