Pain
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Comparative Study
Activated PKA and PKC, but not CaMKIIalpha, are required for AMPA/Kainate-mediated pain behavior in the thermal stimulus model.
Secondary mechanical allodynia resulting from a thermal stimulus (52.5 degrees C for 45s) is blocked by intrathecal (i.t.) pretreatment with calcium-permeable AMPA/KA receptor antagonists, but not NMDA receptor antagonists. Spinal sensitization is presumed to underlie thermal stimulus-evoked secondary mechanical allodynia. We investigated whether this spinal sensitization involves activation and phosphorylation of calcium-dependent protein kinases (PKA, PKC and CaMKIIalpha), and examined if the noxious stimulus increases phosphorylated AMPA GLUR1 (pGLUR1 Ser-845 and pGLUR1 Ser-831). ⋯ Although thermal stimulation did not change either pGLUR1 Ser-845 or pGLUR1 Ser-831, it was associated with an increase in cytosolic total GLUR1. Pretreatment with a selective calcium-permeable AMPA/KA receptor antagonist (5nmol joro spider toxin), but not an NMDA receptor antagonist (25nmol d-2-amino-5-phosphonovalerate, AP-5), blocked thermal stimulus-evoked increases in phosphorylated PKA and PKC, in addition to increased cytosolic GLUR1. These findings indicate that spinal sensitization in the thermal stimulus model does not involve CaMKIIalpha activation or AMPA GLUR1 receptor phosphorylation, and differs from that occurring in NMDAr-dependent pain states.
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Comparative Study
Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord.
In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat peripheral neuropathic pain models the presynaptic inhibitory effect of the mu opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory postsynaptic currents (EPSCs) and miniature EPSCs in superficial dorsal horn neurons is substantially reduced, but only in those spinal cord segments innervated by injured primary afferents. The two nerve injury models also reduce the postsynaptic potassium channel opening action of DAMGO on lamina II spinal cord neurons, but again only in segments receiving injured afferent input. The inhibitory action of DAMGO on ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons is also reduced in affected segments following nerve injury. ⋯ Decreased activation of MOR on injured primary afferent central terminals and the second order neurons they innervate may minimize any reduction by opioids of the spontaneous pain mediated by ectopic input from axotomized small diameter afferents. Retention of MOR expression and activity in nearby non-injured afferents will enable, however, an opioid-mediated reduction of stimulus-evoked and spontaneous pain carried by intact nociceptor afferents and we find that intrathecal DAMGO (1000 ng) reduces mechanical hypersensitivity in rats with SNL. Axotomy-induced changes in MOR may contribute to opioid- insensitive components of neuropathic pain while the absence of these changes in intact afferents may contribute to the opioid sensitive components.
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We developed a mouse model of cancer pain to investigate its underlying mechanisms. SCC-7, squamous cell carcinoma (SCC) derived from C3H mice, was inoculated subcutaneously into either the plantar region or thigh in male C3H/Hej mice. Heat and mechanical sensitivity as well as spontaneous behavior were measured at the plantar surface of the ipsilateral hind paw after the inoculation. ⋯ Intraperitoneal administration of the competitive TRPV1 antagonist capsazepine inhibited hyperalgesia induced by tumor cell-inoculation in either plantar- or thigh-inoculated animals. This study indicated that inoculation of SCC resulted in spontaneous pain, heat hyperalgesia and mechanical allodynia. The altered expression of TRPV1 in the DRG may be involved in behavioral changes in this model.
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Randomized Controlled Trial Comparative Study Clinical Trial
Effects of intradermal foot and forearm capsaicin injections in normal and vulvodynia-afflicted women.
Cutaneous response to capsaicin has been used to assess central sensitization in pain research. This study compared the response to intradermal capsaicin in the forearm and foot of vulvar vestibulitis (vestibulodynia)-afflicted cases and controls. We hypothesized that cases will experience greater spontaneous pain, larger cutaneous areas of punctate hyperalgesia and dynamic allodynia, and greater vascular flow than controls. ⋯ VVS cases had higher resting pulse rates and lower resting systolic blood pressures than in controls. Conclusion. VVS patients show enhancement of post-capsaicin pain response extending far beyond the anatomic location of the primary complaint.
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Comparative Study
Passive coping is a risk factor for disabling neck or low back pain.
Despite evidence suggesting that coping is an important concept in the study of pain, its role in predicting the development of disabling pain has not been previously studied. To assess the relationship between coping and the development of disabling pain. ⋯ Passive coping is a strong and independent predictor of disabling neck and/or back pain. This strong relationship identifies passive coping as a marker for risk of disability and can allow for the identification of individuals at risk and in need of intervention to aid in improving their overall adjustment.