The journal of pain : official journal of the American Pain Society
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Preterm neonates exposed to painful procedures in the neonatal intensive care unit exhibit increased pain scores and alterations in oxygenation and heart rate. It is unclear whether these physiological responses increase the risk of oxidative stress. Using a prospective study design, we examined the relationship between a tissue-damaging procedure (TDP; tape removal during discontinuation of an indwelling central arterial or venous catheter) and oxidative stress in 80 preterm neonates. Oxidative stress was quantified by measuring uric acid (UA) and malondialdehyde (MDA) concentration in plasma before and after neonates (n = 38) experienced a TDP compared to those not experiencing any TDP (control group, n = 42). Pain was measured before and during the TDP using the Premature Infant Pain Profile (PIPP). We found that pain scores were higher in the TDP group compared to the control group (median scores, 11 and 5, respectively; P < .001). UA significantly decreased over time in control neonates but remained stable in TDP neonates (132.76 to 123.23 μM versus 140.50 to 138.9 μM; P = .002). MDA levels decreased over time in control neonates but increased in TDP neonates (2.07 to 1.81 μM versus 2.07 to 2.21 μM, P = .01). We found significant positive correlations between PIPP scores and MDA. Our data suggest a significant relationship between procedural pain and oxidative stress in preterm neonates. ⋯ This article presents data describing a significant relationship between physiological markers of neonatal pain and oxidative stress. The method described in this paper can potentially be used to assess the direct cellular effects of procedural pain as well the effectiveness of interventions performed to decrease pain.
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The hippocampus is believed to play an important role in sex-based differences of pain perception. Whether estrogen potentiates allodynia in the inflamed temporomandibular joint (TMJ) through affecting the expressions of pain-related genes in the hippocampus remains largely unknown. Because the nerve growth factor (NGF) is an important gene related to inflammatory pain, we tested whether hippocampal NGF may be involved in TMJ inflammatory pain. Here we showed that the rat hippocampal NGF was upregulated by TMJ inflammation induced by complete Freund adjuvant. NGF upregulation was further potentiated by estradiol in a dose-dependent manner. In contrast, NGF transcription in the amygdala, prefrontal cortex, and thalamus was not affected by TMJ inflammation and estradiol. An intrahippocampal injection of NGF antibody or NGF receptor inhibitor K252a (inhibitor for tropomyosin receptor kinase A, TrkA) reduced the allodynia of inflamed TMJ in proestrous rats. Our data suggest that the hippocampal NGF is involved in estradiol-sensitized allodynia of inflammatory TMJ pain. ⋯ We report that complete Freund adjuvant-induced temporomandibular joint (TMJ) inflammation upregulated hippocampal nerve growth factor (NGF) expression, and estradiol replacement potentiated this upregulation. These results propose that estradiol could modulate TMJ pain through the NGF signaling pathway in the hippocampus to exacerbate TMJ pain and offer a possible mechanism of sexual dimorphism of temporomandibular disorder pain.
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Randomized Controlled Trial
"There's more to this pain than just pain": how patients' understanding of pain evolved during a randomized controlled trial for chronic pain.
Chronic pain is prevalent, is costly, and exerts an emotional toll on patients and providers. Little is known about chronic pain in veterans of the recent military conflicts in Afghanistan and Iraq (OEF/OIF/OND [Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn] veterans). This study's objective was to ascertain veterans' perceptions of a multicomponent intervention tested in a randomized controlled trial for OEF/OIF/OND veterans with chronic musculoskeletal pain (ESCAPE: Evaluation of Stepped Care for Chronic Pain). Qualitative interviews were conducted with patients in the intervention arm of ESCAPE. Questions related to veterans' experiences with trial components, overall perceptions of the intervention, strengths, and suggestions for improvement. Twenty-six veterans (21% of total intervention patients) participated. Patients were purposefully sampled to include treatment responders (defined as ≥30% reduction in pain-related disability or pain severity) and non-responders. Non-completers (completed <50% of the trial) were also sampled. Qualitative analysis was guided by grounded theory, using constant comparative methodology. Both responders and non-responders spoke about their evolving understanding of their pain experience during the trial, and how this new understanding helped them to manage their pain more effectively. This evolution is reported under 2 themes: 1) learning to recognize physical and psychosocial factors related to pain; and 2) learning to manage pain through actions and thoughts. ⋯ Responders and non-responders both described making connections between their pain and other factors in their lives, and how these connections positively influenced how they managed their pain. Traditional quantitative measures of response to pain interventions may not capture the full benefits that patients report experiencing.
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Patients with chronic pain experience spontaneous or ongoing pain as well as enhanced sensitivity to evoked stimuli. Spontaneous or ongoing pain is rarely evaluated in preclinical studies. In fact, it remains controversial whether ongoing or spontaneous pain even develops in mice after tissue or nerve injury. This study tested a hypothesis that negative reinforcement can be used to unmask the presence of pain in mice with tissue or nerve injury. We found that spinal administration of clonidine or lidocaine did not elicit conditioned place preference (CPP) in uninjured or sham-operated mice. However, these agents produced CPP in mice with chronic inflammation induced by complete Freund's adjuvant (CFA) or following L5/L6 spinal nerve ligation (SNL). These data indicate the presence of non-evoked (ie, stimulus-independent) ongoing pain in mice with chronic inflammation (CFA) or following nerve injury (SNL). In addition, this study validates the use of negative reinforcement to unmask non-evoked ongoing pain in mice. Given the existence of a large collection of transgenic and knockout mice, our data show the application of this approach to elucidate molecular mechanisms underlying non-evoked pain and to contribute to drug discovery for pain. ⋯ We demonstrated the presence of non-evoked ongoing pain in mice with chronic inflammation or following nerve injury. The study also validates the use of negative reinforcement to unmask non-evoked pain in mice. We propose to apply this approach to identify molecular mechanisms and effective drugs for chronic pain.
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Patients with painful vertebral compression fractures produced by multiple myeloma (MM) often experience reduction in pain after spinal augmentation with kyphoplasty or vertebroplasty. Previous studies have shown pain reduction and improvement in functional status after augmentation, but no studies have examined the effect of augmentation on other cancer-related symptoms. We hypothesized that reduction in pain severity would be significantly associated with improvement in other reported symptoms. We retrospectively studied 79 patients who rated pain and symptom severity both before and after kyphoplasty or vertebroplasty. Pain was significantly reduced after spinal augmentation (1.3 on a 0 to 10 scale; effect size [ES] = .59; P < .001), as were anxiety (1.3; ES = .47), drowsiness (1.3; ES = .39), fatigue (1.1; ES = .32), depression (.7; ES = .28), and difficulty thinking clearly (.7; ES = .26) (all P < .05). Greater reduction in pain was associated with a greater number of symptoms being reduced. Interestingly, insomnia worsened regardless of any amount of improvement in pain. Because appropriate symptom control contributes to the overall well-being of cancer patients, future studies of pain reduction procedures should include measures of other symptoms to fully characterize the potential benefit of treating pain. ⋯ Appropriate symptom control contributes to overall well-being for cancer patients. This study demonstrated that pain reduction after spinal augmentation with vertebroplasty or kyphoplasty was positively associated with reduction in other patient-reported cancer-related symptoms. Future studies of these augmentation procedures should measure multiple symptoms, in addition to pain and functional status.