The journal of pain : official journal of the American Pain Society
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Second messengers mediating the expression of neuroplasticity in a model of chronic pain in the rat.
Hyperalgesic priming is a model of the transition from acute to chronic pain, in which previous activation of cell surface receptors or direct activation of protein kinase C epsilon markedly prolongs mechanical hyperalgesia induced by pronociceptive cytokines. We recently demonstrated a role of peripheral protein translation, alpha-calmodulin-dependent protein kinase II (αCaMKII) activation, and the ryanodine receptor in the induction of hyperalgesic priming. In the present study, we tested if they also mediate the prolonged phase of prostaglandin E2-induced hyperalgesia. We found that inhibition of αCaMKII and local protein translation eliminates the prolonged phase of prostaglandin E2 hyperalgesia. Although priming induced by receptor agonists or direct activation of protein kinase C epsilon occurs in male but not female rats, activation of αCaMKII and the ryanodine receptor also produces priming in females. As in males, the prolonged phase of prostaglandin E2-induced hyperalgesia in female rats is also protein kinase C epsilon-, αCaMKII-, and protein translation-dependent. In addition, in both male and female primed rats, the prolonged prostaglandin E2-induced hyperalgesia was significantly attenuated by inhibition of MEK/ERK. On the basis of these data, we suggest that the mechanisms previously shown to be involved in the induction of the neuroplastic state of hyperalgesic priming also mediate the prolongation of hyperalgesia. ⋯ The data provided by this study suggest that direct intervention on specific targets may help to alleviate the expression of chronic hyperalgesic conditions.
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Multicenter Study Observational Study
Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study.
Aromatase inhibitors (AIs) are the first-line treatment in women with breast cancer for total estrogen depletion. Half the treated women may develop pain, and this condition may therefore be seen as a clinical model of pain related to estrogen deprivation. In this prospective multicenter study, we classified AI-related pain syndromes and identified their predictors. A 1-year, prospective, multicenter cohort study, with 6 visits, was carried out on 135 women with early-stage breast cancer and no pain at the start of AI treatment. At initial assessment, we investigated clinical (demographic and psychosocial, cancer characteristics and treatment, sleep, quality of life), biological (sex hormones, vitamin D, bone biomarkers, oxidative stress, immunologic and inflammatory markers), environmental, and genetic (polymorphism for pain mechanisms) risk factors for pain. During 1 year of follow-up, 77 women (57%) developed pain, leading to AI discontinuation in 12 cases. Five pain syndromes were identified: joint pain (36%), diffuse pain (22%), tendinitis (22%), neuropathic pain (9%), and mixed pain (11%), which are mostly persistent (57%), with diffuse and joint pains the most intense. Risk factors for the development of pain included higher levels of anxiety and impaired quality of life at the initial assessment, whereas cancer characteristics, genetic background, inflammation, and immunologic and hormonal status at baseline were not significant predictors. ⋯ This article presents a classification of AI-related pain syndromes induced by estrogen deprivation that were previously described as arthralgia, but not as neuropathic, diffuse, and mixed pain. This estrogen deprivation-related condition represents a clinical model of pain, and our study identified mostly psychological risk factors for pain development.
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Scientific models are like tools, and like any tool they can be evaluated according to how well they achieve the chosen goals of the task at hand. In the science of treatment development for chronic pain, we might say that a good model ought to achieve at least 3 goals: 1) integrate current knowledge, 2) organize research and treatment development activities, and 3) create progress. In the current review, we examine models underlying current cognitive behavioral approaches to chronic pain with respect to these criteria. A relatively new model is also presented as an option, and some of its features examined. This model is called the psychological flexibility model. This model fully integrates cognitive and behavioral principles and includes a process-oriented approach of treatment development. So far it appears capable of generating treatment applications that range widely with regard to conditions targeted and modes of delivery and that are increasingly supported by evidence. It has led to the generation of innovative experiential, relationship-based, and intensive treatment methods. The scientific strategy associated with this model seeks to find limitations in current models and to update them. It is assumed within this strategy that all current treatment approaches will one day appear lacking and will change. ⋯ This Focus Article addresses the place of theory and models in psychological research and treatment development in chronic pain. It is argued that such models are not merely an academic issue but are highly practical. One potential model, the psychological flexibility model, is examined in further detail.
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Observational Study
Attachment styles, pain, and the consumption of analgesics during labor: a prospective observational study.
Individuals with less secure attachment styles have been shown to experience more pain than people with more secure attachment styles; however, attachment styles have not yet been examined in the context of labor pain and analgesic consumption. The purpose of this prospective observational study was to assess the influence of the mother's attachment style on the perception of labor pain, as assessed by a visual analog scale and analgesic consumption. Eighty-one pregnant women with a mean age of 32 years (standard deviation = 5.1) were assessed during the third trimester of pregnancy and during labor. The physical predictors of labor pain were recorded, and the adult attachment style was assessed with the Adult Attachment Scale-Revised. For labor analgesia, a low dose of patient-controlled epidural analgesia protocol (ropivacaine .6 mg/mL plus sufentanil .5 μg/mL) was used. Women with a secure attachment style reported significantly less labor pain (P < .001) and a significantly lower analgesic consumption during labor (P < .001) than insecurely attached women. These findings suggest that women's attachment style was associated with labor pain and analgesic consumption and support the relevance of the attachment theory as a promising conceptual framework for understanding labor pain. ⋯ This study showed that women with an insecure attachment style were more likely to report higher pain before patient-controlled epidural analgesia and higher analgesic consumption and to request supplemental analgesia during labor. The assessment of adult attachment has the potential to identify women at high risk of poorly coping with pain during childbirth.
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This study tested the effects of aging and race on responses to noxious stimuli using a wide range of stimulus modalities. The participants were 53 non-Hispanic blacks and 138 non-Hispanic white adults, ages 45 to 76 years. The participants completed a single 3-hour sensory testing session where responses to thermal, mechanical, and cold stimuli were assessed. The results suggest that there are selected age differences, with the older group less sensitive to warm and painful heat stimuli than middle-aged participants, particularly at the knee. This site effect supports the hypothesis that the greatest decrement in pain sensitivity associated with aging occurs in the lower extremities. In addition, there were several instances where age and race effects were compounded, resulting in greater race differences in pain sensitivity among the older participants. Overall, the data suggest that previously reported race differences in pain sensitivity emerged in our older samples, and this study contributes new findings in that these differences may increase with age in non-Hispanic blacks for temporal summation and both heat and cold immersion tolerance. We have added to the aging and pain literature by reporting several small to moderate differences in responses to heat stimuli between middle- and older-age adults. ⋯ This study found that the greatest decline in pain sensitivity with aging occurs in the lower extremities. In addition, race differences in pain sensitivity observed in younger adults were also found in our older sample.