European journal of pain : EJP
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The N-methyl-d-aspartate receptor (NMDAR) contributes to central sensitization in the spinal cord, a phenomenon which comprises various pathophysiological mechanisms responsible for neuropathic pain-like signs in animal models. NMDAR function is modulated by post-translational modifications including phosphorylation, and this is proposed to underlie its involvement in the production of pain hypersensitivity. As in diabetic patients, streptozotocin-induced diabetic rats exhibit or not somatic mechanical hyperalgesia; these rats were named DH and DNH respectively. ⋯ Western-blots analysis showed no change in NR1 protein levels, whatever the behavioural and glycemic status of the animals. Chronic intrathecal treatment (5μg/rat/day for 7days) by U0126 and MK801, which blocked MEK (an upstream kinase of extracellular signal-regulated protein kinase: ERK) and the NMDAR respectively, simultaneously suppressed somatic mechanical hyperalgesia developed by diabetic rats and decreased pNR1. These results indicate for the first time that increased expression of pNR1 is regulated by ERK and the NMDAR via a feedforward mechanism in spinal neurons and microglia and represents one mechanism involved in central sensitization and somatic mechanical hyperalgesia after diabetes.
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Tonic pain in one body segment can inhibit the perception of pain in another body segment. This phenomenon is mediated by diffuse noxious inhibitory controls (DNIC), and its efficacy in craniofacial regions is investigated in this study. A compressive device that evoked a tonic, moderate/severe, headache-like, conditioning pain (∼8/10 on a visual analogue scale) was applied for 15min. ⋯ PPTol was unchanged. In the period after the painful conditioning stimulation PPT was depressed compared to control. This study shows that pain evoked from the craniofacial region evokes DNIC-like mechanisms on segmental as well as heterosegmental sites.
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The aim of this study was to determine whether peripheral N-methyl-d-aspartate (NMDA) receptors are involved in inflammation-induced mechanical hypersensitivity of the temporomandibular joint (TMJ) region. We developed a rat model of mechanical sensitivity to Complete Freund's Adjuvant (CFA; 2μl containing 1μg Mycobacterium tuberculosis)-induced inflammation of the TMJ and examined changes in sensitivity following injection of NMDA receptor antagonists (dl-2-amino-5-phosphonovaleric acid (AP5) or Ifenprodil) with CFA. CFA injected into the TMJ resulted in an increase in mechanical sensitivity relative to pre-injection that peaked at day 1 and lasted for up to 3days (n=8, P<0.05). ⋯ Immunohistochemical studies showed that 99% and 28% of trigeminal ganglion neurons that innervated the TMJ contained the NR1 and NR2B subunits respectively. Our findings suggest a role for peripheral NMDA receptors in inflammation-induced pain of the TMJ region. Targeting peripheral NMDA receptors with peripheral application of NMDA receptor antagonists could provide therapeutic benefit and avoid side effects associated with blockade of NMDA receptors in the central nervous system.
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Pain self-efficacy and fear of movement have been proposed to explain how pain can lead to disability for patients with chronic low back pain. However the extent to which pain self-efficacy and fear of movement mediate the relationship between pain and disability over time has not been investigated. This study aimed to investigate whether pain self-efficacy and/or fear of movement mediate the relationship between pain intensity and disability in patients with recent onset chronic low back pain. ⋯ However, in the longitudinal analyses, only improvements in self-efficacy beliefs partially mediated the relationship between changes in pain and changes in disability over a 12months period. We found no support for the theory that fear of movement beliefs mediate this relationship. Therefore, we concluded that pain self-efficacy may be a more important variable than fear of movement beliefs in terms of understanding the relationship between pain and disability.
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Although spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain, pain relief is still not successful in a large group of patients. We suggest that the success of SCS may be related to the timing of SCS during the development of chronic neuropathic pain. We therefore compared the effect of SCS applied after 24h of neuropathic pain (early SCS) and after 16days of neuropathic pain (late SCS). ⋯ In more than half of these animals, pre-stimulation withdrawal thresholds were reached only the next day. Early SCS resulted in an increased number of responders to SCS and furthermore an increased duration of the effect of SCS as compared to late SCS. Early SCS treatment of neuropathic rats is more effective as compared to the late SCS treatment.