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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Randomized Controlled Trial
TENS attenuates repetition-induced summation of activity-related pain following experimentally induced muscle soreness.
This study sought to determine whether repetition-induced summation of activity-related pain (RISP) could be demonstrated in healthy individuals in response to experimentally induced musculoskeletal pain. This study also assessed the effects of transcutaneous electrical nerve stimulation on RISP. The relation between the index of RISP and psychological factors such as catastrophizing and fear of pain was also explored. The sample consisted of 56 healthy (35 women, 21 men) participants who underwent 2 testing sessions, separated by 24 hours. In the first session, musculoskeletal pain was induced with a delayed-onset muscle soreness protocol. During the second session, participants were randomly assigned to the transcutaneous electrical nerve stimulation or placebo condition and were asked to rate their pain as they lifted a series of 18 weighted canisters. An index of RISP was derived as the change in pain ratings across repeated lifts. Approximately 25% of participants showed evidence of RISP. Results also revealed that transcutaneous electrical nerve stimulation attenuated the RISP effect. Psychological measures (fear of pain, catastrophizing) were not significantly correlated with the index of RISP, but the index of RISP was significantly correlated with a measure of physical tolerance. Discussion addresses the clinical implications of the findings as well as the potential mechanisms underlying RISP. ⋯ This study showed that RISP could be demonstrated in healthy individuals in response to experimentally induced musculoskeletal pain with delayed-onset muscle soreness. Transcutaneous electrical nerve stimulation led to a significant reduction in RISP.
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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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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.
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Randomized Controlled Trial
Determinants of pain treatment response and nonresponse: identification of TMD patient subgroups.
The purpose of the present study was to determine if we could identify a specific subtype of temporomandibular disorder (TMD) pain patients that does not respond to treatment. Patients were 101 men and women with chronic TMD pain recruited from the community and randomly assigned to 1 of 2 treatment conditions: a standard conservative care (STD) condition or a standard care plus cognitive-behavioral therapy condition (STD + CBT) in which patients received all elements of STD but also received cognitive-behavioral coping skills training. Growth mixture modeling, incorporating a series of treatment-related predictors, was used to distinguish several distinct classes of responders or nonresponders to treatment based on reported pain over a 1-year follow-up period. Results indicated that treatment nonresponders accounted for 16% of the sample and did not differ from treatment responders on demographics or temporomandibular joint pathology, but that they reported more psychiatric symptoms, poorer coping, and higher levels of catastrophizing. Treatment-related predictors of membership in treatment responder groups versus the nonresponder group included the addition of CBT to STD, treatment attendance, and decreasing catastrophization. It was concluded that CBT may be made more efficacious for TMD patients by placing further emphasis on decreasing catastrophization and on individualizing care. ⋯ This article provides evidence that the TMD chronic pain population is heterogeneous and that a subsample of patients will be unresponsive to standard or psychosocial approaches. The addition of CBT to treatment may be helpful for this group, but new individualized approaches will be needed to treat all patients effectively.