Articles: hyperalgesia.
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TNFalpha plays a pivotal role in rheumatoid arthritis (RA) but little is known of the mechanisms that link the inflammatory and nociceptive effects of TNFalpha. We have established a murine model of TNFalpha-induced TRPV1-dependent bilateral thermal hyperalgesia that then allowed us to identify distinct peripheral mechanisms involved in mediating TNFalpha-induced ipsilateral and contralateral hyperalgesia. Thermal hyperalgesia and inflammation were assessed in both hindpaws following unilateral intraplantar (i.pl.) TNFalpha. ⋯ However, TNFalpha-induced IL-1beta generation in both paws and the presence of local IL-1beta in the contralateral paw were essential for the development of bilateral hyperalgesia. These results identify a series of peripheral events through which TNFalpha triggers and maintains bilateral inflammatory pain. This potentially allows a better understanding of mechanisms involved in TNFalpha-dependent pain pathways in symmetrical diseases such as arthritis.
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Chronic psychological stress is associated with visceral hyperalgesia and increased expression of spinal NK1 receptors (NK1Rs). We aimed to identify the role of spinal microglia in this process. ⋯ This is the first demonstration that stress-induced activation of spinal microglia has a key role in visceral hyperalgesia and associated spinal NK1R up-regulation.
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J. Gastroenterol. Hepatol. · Apr 2009
Antinociceptive effect of chronic lithium on visceral hypersensitivity in a rat model of diarrhea-predominant irritable bowel syndrome: The role of nitric oxide pathway.
Lithium, a widely used drug in bipolar-affective disorders, plays gastro-protective roles. The effects of lithium on several tissues are mediated through nitric oxide (NO), which regulates gastrointestinal motility and mucosal integrity. The aim of this study was to investigate the protective effect of chronic lithium administration on visceral hypersensitivity and to investigate the role of NO as a potential mechanism of lithium in a rat model of irritable bowel syndrome. ⋯ The results indicate the antinociceptive property of chronic lithium on visceral hypersensitivity. As this effect was lowered by NOS inhibitors, NO might play a role in the protective effect of lithium to some extent.
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Clin. Exp. Pharmacol. Physiol. · Apr 2009
Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.
1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. ⋯ The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.
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The facet joint is a common source of pain in both the neck and low back, and can be injured by abnormal loading of the spinal joints. Whereas a host of nociceptive changes including neuronal activation, neuropeptide expression, and inflammatory mediator responses has been reported for rat models of joint pain, no such responses have been explicitly investigated or quantified for painful mechanical injury to the facet joint. Two magnitudes of joint loading were separately imposed in a rat model of cervical facet joint distraction: Painful and nonpainful distractions. Behavioral outcomes were defined by assessing mechanical hyperalgesia in the shoulders and forepaws. Substance P (SP) mRNA and protein levels were quantified in the dorsal root ganglion (DRG) and spinal cord at days 1 and 7 following distraction. Painful distraction produced mechanical hyperalgesia that was significantly greater (P < .010) than that for a nonpainful distraction. Painful distraction significantly increased spinal SP mRNA (P = .048) and SP protein expression in the DRG (P = .013) at day 7 compared to nonpainful distraction. However, spinal SP protein for painful distraction was significantly less (P = .024) than that for nonpainful distraction at day 1. Joint distractions producing different behavioral outcomes modulate SP mRNA and protein in the DRG and spinal cord, suggesting that SP responses may be involved with different temporal responses in painful joint loading. ⋯ SP mRNA and protein in the DRG and spinal cord are quantified at 2 time points after cervical facet joint distractions that separately do or do not produce mechanical hyperalgesia. Studies describe a role for SP to contribute to pain produced by mechanical joint loading.