The journal of pain : official journal of the American Pain Society
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Several lines of evidence indicate that brain-derived neurotrophic factor (BDNF) plays a key role as a central pronociceptive modulator of pain, acting through postsynaptic TrkB receptors that trigger intracellular signaling cascades leading to central sensitization. The overall aim of this study was to investigate to what extent BDNF could participate in the generation and maintenance of trigeminal neuropathic pain. The results showed that acute intracisternal administration of nanogram doses of BDNF in naïve mice elicited long-lasting, dose-related, cold allodynic responses to topical application of acetone onto vibrissal pad skin. The systemic administration of cyclotraxin-B (CTX-B), a new TrkB receptor antagonist, or propentofylline, an inhibitor of glial activation, was able to either prevent or reverse the effects of intracisternal BDNF on cold nociception. In addition, the blockade of TrkB receptor by CTX-B inhibited the mechanisms that either initiate or maintain cold allodynia in the ipsilateral vibrissal pad skin after unilateral constriction of the infraorbital nerve. These observations raise the possibility that BDNF is capable on its own of conveying many features of the signaling mechanisms that underlie central sensitization caused by nerve constriction. ⋯ Although further studies are necessary to examine in detail the mechanisms underlying the strong anti-allodynic action of CTX-B, this compound may represent an interesting lead for the development of novel therapeutic strategies aimed at preventing and/or suppressing central sensitization associated with neuropathic pain.
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Recently, the lexicon of pain was refined into a parsimonious set of words making up the Pain Descriptor System (PDS). The present study investigated the latent structure of the sensory category of the PDS with its 24 descriptors distributed equally across 8 subcategories. A sample of 629 chronic pain patients rated the degree to which each of these words described their pain. It was found that coldness-related words were rarely used and shared high covariance with other descriptors, thus warranting their removal as a subcategory. Confirmatory factor analysis of a previously theorized single higher-order model of 7 latent factors (each with 3 observed variables) resulted in poor fit, x(2)(181) = 377.72, P < .05; comparative fit index (CFI) = .915; root mean square error of approximation (RMSEA) = .04. This model was replaced with a dual higher-order model retaining the same 7 latent factors plus 2 higher-order factors corresponding to deep pain versus superficial pain. This model provided a good representation of the data, x(2)(181) = 301.07, P < .05; CFI = .948; RMSEA = .032. Therefore, descriptors of pain sensation differentiate sensory quality while also reflecting a fundamental dichotomy supported by neurophysiological research. Thus, the lexicon can illuminate pathophysiology, thereby clarifying pain diagnoses. ⋯ Confirmatory factor analysis was performed on pain sensation descriptors used by 629 patients. This supported a hierarchical model with 7 lower-order factors plus 2 higher-order factors corresponding to deep pain versus superficial pain. By reflecting neurophysiology, this lexicon of pain can offer diagnostic clues.
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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 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.
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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.