Articles: hyperalgesia.
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Decreased spinal cord GABAergic inhibition is a major contributor to the persistent neuropathic pain that can follow peripheral nerve injury. Recently, we reported that restoring spinal cord GABAergic signaling by intraspinal transplantation of cortical precursors of GABAergic interneurons from the embryonic medial ganglionic eminence (MGE) can reverse the mechanical hypersensitivity (allodynia) that characterizes a neuropathic pain model in the mouse. ⋯ Transplants from these mice, in which GABA is synthesized but cannot be stored or released, had no effect on mechanical hypersensitivity or heat hyperalgesia in the paclitaxel model. Taken together, these results demonstrate the therapeutic potential of GABAergic precursor cell transplantation in diverse neuropathic pain models and support our contention that restoration of inhibitory controls through release of GABA from the transplants is their mode of action.
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Cutaneous allodynia (CA) is a characteristic of central sensitization, predicting migraine progression, and poor response to therapy. The present study aimed to find out the cerebral functional alterations related to the establishment of central sensitization in migraineurs using functional magnetic resonance imaging (fMRI). ⋯ The interictal dysfunction of pain processing pathway may be responsible for (at least relevant to) central sensitization in migraine patients, via abnormal modulations of nociceptive transmission.
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Neuroscience research · Jun 2015
Modulation of spinal glial reactivity by intrathecal PPF is not sufficient to inhibit mechanical allodynia induced by nerve crush.
Spinal glial reactivity has been strongly implicated in pain that follows peripheral nerve injury. Among the many therapeutic agents that have been tested for anti-allodynia through immune modulation is the atypical methylxanthine propentofylline. ⋯ Microglial/macrophage Iba-1 and astrocytic GFAP expression, increased in the dorsal horn of nerve crushed animals, was, however, effectively attenuated by propentofylline. Effective modulation of spinal glial reactivity is, thus, no assurance for anti-allodynia.
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The hyperalgesic effects of long-term opioid use in community-dwelling adults with chronic pain have not been widely reported. Therefore, the primary aim of this study was to determine the associations between opioid use and heat pain (HP) perception in a sample of community-dwelling adults with chronic pain. The study cohort involved 187 adults (85 opioid and 102 nonopioid) with chronic pain consecutively admitted to an outpatient interdisciplinary pain treatment program. ⋯ In univariable (P = 0.019) and multiple variable (P = 0.003) linear regression analyses (adjusted for age, sex, body mass index, work status, pain diagnosis, pain severity, depression, and pain catastrophizing), opioid use was associated with lower (more hyperalgesic) nonstandardized values of HP 5-0.5. Similarly, in univariable (P = 0.004) and multiple variable (P = 0.011) linear regression analyses (adjusted for work status, pain diagnosis, pain severity, depression, and pain catastrophizing), opioid use was associated with lower standardized values of HP 5-0.5. In this sample of community-dwelling adults, these observations suggest that long-term opioid use was associated with hyperalgesia independent of other clinical factors known to influence HP perception.
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Randomized Controlled Trial
Altered thermal grill response and paradoxical heat sensations after topical capsaicin application.
The thermal grill illusion, where interlaced warm and cold bars cause an unusual burning sensation, and paradoxical heat sensations (PHS), where cold is perceived as warm when alternating warm and cold, are examples of a complex integration of thermal sensations. Here, we investigated the effect of sensitization of heat-sensitive neurons on cold and warm integration. We examined thermal thresholds, PHS, and warm, cold, and pain sensations to alternating cold (10°C) and warm (40°C) bars (the thermal grill [TG]) in the primary area (application site) after topical application with capsaicin and vehicle control (ethanol) on the volar forearms in randomized order in 80 healthy participants. ⋯ Paradoxical heat sensation was only seen in 3 participants after control application but in 19 participants after capsaicin. Those with PHS after capsaicin application had higher detection thresholds to both cold and warm than those without PHS, but there was no difference in thermal pain threshold. These results suggest that a complex cross talk among several cold and warm sensitive pathways shapes thermal perception.