Pain
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Comparative Study
Results availability for analgesic device, complex regional pain syndrome, and post-stroke pain trials: comparing the RReADS, RReACT, and RReMiT databases.
Evidence-based medicine rests on the assumption that treatment recommendations are robust, free from bias, and include results of all randomized clinical trials. The Repository of Registered Analgesic Clinical Trials search and analysis methodology was applied to create databases of complex regional pain syndrome (CRPS) and central post-stroke pain (CPSP) trials and adapted to create the Repository of Registered Analgesic Device Studies databases for trials of spinal cord stimulation (SCS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). We identified 34 CRPS trials, 18 CPSP trials, 72 trials of SCS, and 92 trials of rTMS/tDCS. ⋯ Results availability is higher 12 months after study completion but remains below 60% for peer-reviewed publications. Recommendations to increase results availability include supporting organizations advocating for transparency, enforcing existing results reporting regulations, enabling all primary registries to post results, stating trial registration numbers in all publication abstracts, and reducing barriers to publishing "negative" trials. For all diseases and treatment modalities, evidence-based medicine must rigorously adjust for the sheer magnitude of missing results in formulating treatment recommendations.
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Pain-related depression of behavior and mood is a key therapeutic target in the treatment of pain. Clinical evidence suggests a role for decreased dopamine (DA) signaling in pain-related depression of behavior and mood. Similarly, in rats, intraperitoneal injection of dilute lactic acid (IP acid) serves as a chemical noxious stimulus to produce analgesic-reversible decreases in both (1) extracellular DA levels in nucleus accumbens (NAc) and (2) intracranial self-stimulation (ICSS), an operant behavior reliant on NAc DA. ⋯ In the absence of the noxious stimulus, amitifadine increased NAc levels of both DA and serotonin, and behaviorally, amitifadine produced significant but weak abuse-related ICSS facilitation. Moreover, amitifadine was more potent to block IP acid-induced depression of ICSS than to facilitate control ICSS. These results support consideration of amitifadine and related monoamine uptake inhibitors as candidate analgesics for treatment of pain-related behavioral depression.
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Pain modulation efficiency delays seeking medical help in patients with acute myocardial infarction.
Rapid reperfusion is crucial to reduce mortality in patients with ST elevation myocardial infarction. Prehospital patient delay, defined as time from symptoms onset to the decision to seek medical attention, accounts for a large proportion of cases with delayed reperfusion. However, whether pain modulation processes are involved in this phenomenon is not known. ⋯ Multivariable regression analysis (R = 0.449; P < 0.0001) revealed an inverse independent association between chest pain intensity (P < 0.001) and patient delay, whereas efficient CPM was positively associated with prolonged patient delay (P = 0.034). The electrocardiography-derived myocardial ischemic area was not associated with chest pain intensity or patient delay, indicating that the affected ischemic tissue is not a dominant component that determines pain response. In conclusion, beyond the perceived chest pain intensity, the activation pattern of descending inhibition pathways during coronary occlusion affects pain interpretation and behavior during acute coronary occlusion.
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Neuropathic pain is one of the most difficult consequences of spinal cord injury (SCI). The clinical correlates of the underlying mechanisms responsible for neuropathic pain are not well understood, although methods such as quantitative somatosensory testing (QST) or brain imaging have been used to further a mechanism-based understanding of pain. Our previous SCI study demonstrated a significantly lower glutamate-glutamine/myo-inositol ratio (Glx/Ins) in the anterior cingulate cortex in persons with severe neuropathic pain compared with those with less severe neuropathic pain or pain-free, able-bodied controls, suggesting that a combination of decreased glutamatergic metabolism and glial activation may contribute to the development of severe neuropathic pain after SCI. ⋯ A cluster analysis including SCI participants resulted in 1 group (n = 19) with significantly (P < 0.001) greater pain intensity (6.43 ± 1.63; high neuropathic pain [HNP], and lower Glx/Ins [1.22 ± 0.16]) and another group (n = 35) with lower pain intensity ratings (1.59 ± 1.52, low neuropathic pain [LNP], and higher Glx/Ins [1.47 ± 0.26]). After correcting for age, QST indicated significantly greater somatosensory function in the HNP group compared with the LNP group. Our results are consistent with research suggesting that damage to, but not abolition of, the spinothalamic tract contributes to development of neuropathic pain after SCI and that secondary inflammatory processes may amplify residual spinothalamic tract signals by facilitation, disinhibition, or sensitization.
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The number of patients suffering from postoperative pain due to orthopedic surgery and bone fracture is projected to dramatically increase because the human life span, weight, and involvement in high-activity sports continue to rise worldwide. Joint replacement or bone fracture frequently results in skeletal pain that needs to be adequately controlled for the patient to fully participate in needed physical rehabilitation. Currently, the 2 major therapies used to control skeletal pain are nonsteroidal anti-inflammatory drugs and opiates, both of which have significant unwanted side effects. ⋯ Administration of anti-nerve growth factor before orthopedic surgery or after bone fracture attenuated skeletal pain behaviors by 40% to 70% depending on the end point being assessed. These data suggest that nerve growth factor is involved in driving pain due to orthopedic surgery or bone fracture. These animal models may be useful in developing an understanding of the mechanisms that drive postoperative orthopedic and bone fracture pain and the development of novel therapies to treat these skeletal pains.