Articles: hyperalgesia.
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Eur. J. Nucl. Med. Mol. Imaging · Dec 2007
Controlled Clinical TrialFollow-up of pain processing recovery after ketamine in hyperalgesic fibromyalgia patients using brain perfusion ECD-SPECT.
The aim of this study was to determine whether the follow-up of pain processing recovery in hyperalgesic fibromyalgia (FM) could be objectively evaluated with brain perfusion ethyl cysteinate dimer single photon computerized tomography (ECD-SPECT) after administration of ketamine. ⋯ This prospective study suggests that blockade of facilitatory descending modulation of pain with ketamine can be evaluated in the periaqueductal grey with brain perfusion SPECT.
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Severe burn induces severe pain. While chronic as well as acute pain syndromes are reported, the peripheral mechanisms of burn-induced chronic pain syndromes have not been studied. We tested the hypothesis that burn induces plastic changes in primary afferent nociceptors that predispose to chronic pain states. ⋯ After recovery, local injection of prostaglandin E2 (PGE2), to mimic re-injury, induced an enhanced and markedly prolonged mechanical hyperalgesia compared to the hyperalgesic effect of PGE2 in the control contralateral paw. This prolonged PGE2-induced hyperalgesia was reversed by a selective inhibitor of protein kinase C-epsilon (PKCepsilon). Our findings suggest PKCepsilon as a peripheral mechanism for burn-induced chronic pain syndromes.
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Pharmacol. Biochem. Behav. · Dec 2007
Milnacipran attenuates hyperalgesia and potentiates antihyperalgesic effect of tramadol in rats with mononeuropathic pain.
Milnacipran is a non-tricyclic antidepressant drug which selectively inhibits serotonin and noradrenaline re-uptake and is recommended in the treatment of various chronic pain syndromes. Many studies have shown that compounds known to block monoamine uptake potentiate the antinociceptive effects of opioids. This study investigates the effect of milnacipran alone or in combination with an opiodergic drug, i.e. tramadol, on hyperalgesia in a rat model of neuropathic pain. ⋯ Intraperitoneal acute injection of milnacipran 60 mg/kg produced an antihyperalgesic effect which was prevented by pretreating systemically with alpha-methyl-p-tyrosine, an inhibitor of noradrenaline synthesis; parachlorophenylalanine, an inhibitor of serotonin synthesis; and naloxone, an antagonist of opioidergic receptors. Co-administration of milnacipran 40 mg/kg with tramadol (20 and 40 mg/kg) potentiated the antihyperalgesic effect of tramadol. Milnacipran has an antihyperalgesic effect mediated by serotonergic, noradrenergic and opioidergic systems and the combined use of tramadol with milnacipran potentiates the effect of tramadol in the management of neuropathic pain.
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We have previously demonstrated that gabapentin supraspinally activates the descending noradrenergic system to alleviate neuropathic pain. In this study, we investigated whether pregabalin, an antiepileptic and analgesic drug that is also designed as a structural analogue of gamma-aminobutyric acid (GABA), exhibits supraspinal analgesic effects similar to those of gabapentin involving the descending noradrenergic system. Both systemically (intraperitoneally; i.p.) and locally (intracerebroventricularly or intrathecally; i.c.v. or i.t.) injected pregabalin reduced thermal and mechanical hypersensitivity in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve (the Seltzer model), suggesting that pregabalin acts at both supraspinal and spinal loci. ⋯ Depletion of spinal noradrenaline (NA) or pharmacological blockade of spinal alpha(2)-adrenoceptors with yohimbine (i.p. or i.t.), but not alpha(1)-adrenoceptors with prazosin (i.p.), reduced the analgesic effects of pregabalin (i.p. or i.c.v.) on thermal and mechanical hypersensitivity. Moreover, i.c.v.-administered pregabalin dose-dependently increased the spinal 4-hydroxy-3-methoxyphenylglycol (MHPG) content and the MHPG/NA ratio only in mice with neuropathic pain, whereas the concentrations of NA, serotonin, 5-hydroxyindoleacetic acid and dopamine were unchanged, demonstrating that supraspinal pregabalin accelerated the spinal turnover of NA. Together, these results indicate that pregabalin supraspinally activates the descending noradrenergic pain inhibitory system coupled with spinal alpha(2)-adrenoceptors to ameliorate neuropathic pain.
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Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.
Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. ⋯ This was in contrast to the numerous changes in A delta-fibers: the percentage of L4 cold sensitive A delta-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive A delta-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 A delta-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both A delta- and C-uninjured fibers, but A delta fibers appear to provide a major contribution to cold hypersensitivity in neuropathic rats.