Pain
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N-methyl-D-aspartate (NMDA) receptors serve prominent roles in vast physio-pathological conditions including hyperalgesia (defined as augmented pain intensity in response to painful stimuli) associated with central sensitization. Using M40403 a synthetic low molecular weight superoxide dismutase mimetic that removes superoxide we show for the first time that this radical plays a key role in NMDA-mediated hyperalgesia. Intrathecal administration of NMDA in rats led to a time-dependent development of thermal hyperalgesia. ⋯ M40403 by preventing MnSOD nitration restored its activity and inhibited the hyperalgesic response to intrathecal NMDA. Thus, superoxide-mediated nitration and deactivation of spinal MnSOD is a novel pathway of NMDA-mediated spinal hyperalgesia and hence central sensitization since it helps to maintain high levels of superoxide that in turn maintains nociceptive signaling. The broader implication of our findings is that superoxide may contribute to various forms of pain events that are driven by NMDA-receptor activation.
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Peripheral nerve injury leads to structural and functional changes in the spinal dorsal horn, and these are thought to be involved in the development of neuropathic pain. In the chronic constriction injury (CCI) model, abnormal 'dark' neurons and apoptotic nuclei have been observed in laminae I-III of the dorsal horn in the territory innervated by the injured sciatic nerve. These findings have been taken as evidence that there is significant neuronal death in this model, and it has been suggested that loss of inhibition resulting from death of GABAergic inhibitory interneurons contributes to the neuropathic pain. ⋯ All of the CCI animals showed clear signs of thermal hyperalgesia. However, the numbers of neurons in laminae I-III of the ipsilateral dorsal horn in these animals did not differ significantly from those on the contralateral side, nor from those of sham-operated or naïve animals. These results do not, therefore, support the suggestion that there is significant neuronal death in the dorsal horn in this model.
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Comparative Study
Gender differences in pain, coping, and mood in individuals having osteoarthritic knee pain: a within-day analysis.
This study examined gender differences in prospective within-day assessments of pain, pain coping, and mood in men and women having OA, and analyzed gender differences in dynamic relations between pain, mood, and pain coping. A sample of 64 women and 36 men diagnosed as having pain due to osteoarthritis of the knee(s) rated their pain, pain coping, and mood two times each day (once in the afternoon and once in the evening) for 30 days using a booklet format. Two gender differences were found in between person-analyses: women used more problem focused coping than men, and women who catastrophized were less likely than men to report negative mood. ⋯ Third, men were more likely than women to use emotion-focused coping when their mood was more negative. Finally, men were more likely than women to experience an increase in negative mood and a decrease in positive mood in the morning after an evening of increased pain. Taken together, these findings underscore the importance of obtaining multiple daily assessments when studying gender differences in the pain experience.
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Comparative Study
Pain catastrophizing and social support in married individuals with chronic pain: the moderating role of pain duration.
In the current study, 96 married chronic pain patients were recruited from the community to test hypotheses about the roles of catastrophizing and psychological distress in relation to perceived support from close others. It was expected that pain duration would moderate the relationship between catastrophizing and perceived support and between catastrophizing and psychological distress. In addition, distress was hypothesized to mediate the relationship between the pain duration-catastrophizing interaction and support. ⋯ Pain duration did not interact with catastrophizing in relating to psychological distress, which precluded the examination of distress as a mediator between the pain duration-catastrophizing interaction and support. Moreover, psychological distress did not significantly mediate the relationships between pain catastrophizing and perceived support. These findings are discussed in the context of cognitive-behavioral and interpersonal perspectives of pain.
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Comparative Study
c-fos and CRF receptor gene transcription in the brain of acetic acid-induced somato-visceral pain in rats.
We aimed to characterize neuronal and corticotrophin-releasing (CRF) pathways in a model of somato-visceral pain in rats. Male rats received an intraperitoneal (i.p.) injection of either vehicle (controls) or acetic acid (AA) and were sacrificed 1, 2, 3, 4, or 6 h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF(1), CRF(2 alpha,beta) receptors were assayed by in situ hybridisation histochemistry. ⋯ In contrast, no expression of CRF(2) transcripts was observed in the PVN either in basal conditions or after AA i.p. These data argue for an activation of CRF pathways within the PVN in this model of somato-visceral pain. The use of CRF antagonists, particularly of the CRF(1) type, should have an interest in somato-visceral pain pathology.