Articles: hyperalgesia.
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Journal of anesthesia · Dec 2011
Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by painful nerve injury in rats.
The neurosteroid allopregnanolone (AP) influences the excitability of the central nervous system by acting as a positive allosteric modulator of γ-aminobutyric acid type A (GABA(A)) receptors. Here, we investigated the role of AP and its therapeutic potential in rats that showed hyperalgesic behavior after undergoing spinal nerve ligation (SNL). AP levels measured in the spinal cord and brain of rats that underwent SNL were greater than the corresponding levels in control animals. ⋯ No differences in serum AP levels were observed among the groups. In addition, intrathecal exogenous administration of AP showed the antihyperalgesic effects in hyperalgesic rats after SNL. These findings suggest that changes in spinal AP biosynthesis are involved in the pathogenesis of neuropathic pain following peripheral nerve injury, and pharmacological manipulation of this phenomenon may provide a potential therapeutic target for neuropathic pain.
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Journal of neurotrauma · Dec 2011
Comparative StudyNeuropathy-induced spinal GAP-43 expression is not a main player in the onset of mechanical pain hypersensitivity.
Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. ⋯ Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity.
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Journal of anesthesia · Dec 2011
The effect of intrathecal mu, delta, kappa, and alpha-2 agonists on thermal hyperalgesia induced by mild burn on hind paw in rats.
Mild cutaneous thermal injury, leading to a first-degree burn, induces a sensation of burning pain and enhances the pain sensitivity of the skin. Opioid and α(2) receptor agonists are commonly used to reduce such hyperalgesia. We investigated conditions that induced adequate thermal hyperalgesia in rats and compared the effects of μ, δ, κ, and α(2) receptors at the level of the spinal cord in this model. ⋯ Based on these findings, we could find adequate conditions for thermal hyperalgesia model. In this experimental model, μ, δ, and α(2) receptor agonists produced antinociceptive effects at the level of the spinal cord, but the κ receptor agonist did not.
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Anesthesia and analgesia · Dec 2011
Comparative StudyKnockdown of synaptic scaffolding protein Homer 1b/c attenuates secondary hyperalgesia induced by complete Freund's adjuvant in rats.
Previous studies have demonstrated that Homer 1b/c, a postsynaptic molecular scaffolding protein that binds and clusters metabotropic glutamate receptors at neuronal synapses, has an important role in the metabotropic glutamate receptor signaling process. In the current study, we investigated the possible involvement of Homer 1b/c in secondary hyperalgesia induced by complete Freund's adjuvant (CFA). ⋯ These novel results demonstrate that Homer 1b/c in the spinal cord contributes to the maintenance of secondary hyperalgesia induced by CFA and suggest that Homer 1b/c may be a novel target for pain therapy.
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Behavioural pharmacology · Dec 2011
Intrathecal lemnalol, a natural marine compound obtained from Formosan soft coral, attenuates nociceptive responses and the activity of spinal glial cells in neuropathic rats.
The investigators previously found that the administration of lemnalol, a natural marine compound isolated from the Formosan soft coral Lemnalia cervicorni, produced anti-inflammatory and analgesic effects in carrageenan-injected rats. Recently, several studies have demonstrated that the development and maintenance of neuropathic pain are accompanied by releasing of proinflammatory mediators from activated glial cells in the spinal cord. In this study, we investigated the antinociceptive properties of lemnalol, a potential anti-inflammatory compound, on chronic constriction injury (CCI) in a well-established rat model of neuropathic pain. ⋯ Furthermore, immunohistofluorescence analyses showed that lemnalol (10 μg) also significantly inhibits CCI-induced upregulation of microglial and astrocytic immunohistochemical activation markers in the dorsal horn of the lumbar spinal cord. Double immunofluorescent staining demonstrated that intrathecal injection of lemnalol (10 μg) markedly inhibited spinal proinflammatory mediator tumor necrosis factor-α expression in microglial cells and astrocytes in neuropathic rats. Collectively, our results indicate that lemnalol is a potential therapeutic agent for neuropathic pain, and that further exploration of the effects of lemnalol on glial proinflammatory responses is warranted.