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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Deep brain stimulation (DBS) of the periventricular/periaqueductal gray area and sensory thalamus can reduce pain intensity in patients with neuropathic pain. However, little is known about its impact on quality of life, emotional well-being, and cognition. This study followed up 18 patients who had received DBS for neuropathic pain. Each participant had previously undergone psychometric evaluation of each of the above areas as part of a routine presurgical neuropsychological assessment. Commensurate measures were employed at a follow-up assessment at least 6 months postsurgery. DBS significantly improved mood, anxiety, and aspects of quality of life. Improvements correlated with reduced pain severity. However, the sample continued to show impairments in most areas when compared against normative data published on nonclinical samples. There was little change in general cognitive functioning, aside from deterioration in spatial working memory. However, improvements in pain severity were associated with less improvement (and even deterioration) on measures of executive cognitive functioning. Improvements in emotional well-being also were correlated with changes in cognition. These results suggest that DBS of the periventricular/periaqueductal gray and/or sensory thalamus improves quality of life and emotional well-being in sufferers, although there is some indication of executive dysfunction, particularly among those reporting greatest pain alleviation. ⋯ This article examines the neuropsychological outcomes of DBS surgery as a treatment for neuropathic pain. This intervention was found to improve pain severity, emotional well-being, and quality of life, although such benefits may be accompanied by reduced ability on tasks measuring executive functioning.
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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.
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This study examined the impact of evidence concerning the presence of 1) a biomedical basis for pain and 2) psychosocial influences on practitioner appraisals of patient pain experiences. Furthermore, the potential moderating role of patient pain behavior was examined. In an online study, 52 general practitioners and 46 physiotherapists viewed video sequences of 4 patients manifesting pain, with accompanying vignettes describing presence or absence of medical evidence and psychosocial influences. Participants estimated pain intensity, daily interference, sympathy felt, effectiveness of pain medication, self-efficacy, their likability, and suspicions of deception. Primary findings indicated lower perceived pain and daily interference, less sympathy, lower expectations of medication impact, and less self-efficacy when medical evidence was absent. The same results were found when psychosocial influences were present, but only when the patient displayed higher levels of pain behavior. Furthermore, absence of medical evidence was related to less positive evaluations of the patients and to higher beliefs in deception in both professions. The presence of psychosocial influences was related to less positive evaluations and higher beliefs in deception in both professions. In sum, a range of contextual factors influence health care practitioner responses to patient pain. Implications for caregiving behavior are discussed. ⋯ The present study indicates that in the absence of clear medical evidence and in the presence of psychosocial influences, patient pain might be taken less seriously by health care practitioners. These findings are important to further understand the difficulties that relate to the clinical encounter between pain patients and health care practitioners.