Articles: hyperalgesia.
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Neurochemical research · Oct 2011
Involvement of spinal serotonin receptors in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model.
We previously showed that electroacupuncture (EA) activates medulla-spinal serotonin-containing neurons. The present study investigated the effects of intrathecal 5,7-dihydroxytryptamine creatinine sulfate, a selective neurotoxin for serotonergic terminals, the 5-hydroxytryptamine 1A receptor (5-HT1AR) antagonist NAN-190 hydrobromide and the 5-HT2C receptor (5-HT2CR) antagonist SB-242,084 on EA anti-hyperalgesia. EA was given twice at acupoint GB30 after complete Freund's adjuvant (CFA) injection into hind paw. ⋯ Immunohistochemical staining showed that spinal 5-HT1AR was expressed and that 5-HT2CR was absent in naive and CFA-injected animals 2.5 h post-CFA. These results show a correlation between EA anti-hyperalgesia and receptor expression. Collectively, the data show that EA activates supraspinal serotonin neurons to release 5-HT, which acts on spinal 5-HT1AR to inhibit hyperalgesia.
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Pharmacol. Biochem. Behav. · Oct 2011
Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice.
Fatty acid amide hydrolase (FAAH) is the primary degradative enzyme of the endocannabinoid anandamide (N-arachidonoylethanolamine), which activates cannabinoid CB(1) and CB(2) receptors. FAAH disruption reduces nociception in a variety of acute rodent models of inflammatory pain. The present study investigated whether these actions extend to the chronic, collagen-induced arthritis (CIA) model. ⋯ Similarly, repeated administration of the FAAH inhibitor URB597 reduced CIA severity, and acute administration of rimonabant, but not SR144528, blocked the anti-hyperalgesic effects of prolonged FAAH inhibition, suggesting that prolonged CB(2) receptor activation reduces the severity of CIA, whereas acute CB(1) receptor activation reduces CIA-induced hyperalgesia. In contrast, acute administration of URB597 elicited a CB(1) receptor-dependent anti-hyperalgesic effect. The observed anti-arthritic and anti-hyperalgesic properties of FAAH inhibition, coupled with a lack of apparent behavioral alterations, suggest that endocannabinoid modulating enzymes offer a promising therapeutic target for the development of novel pharmacological approaches to treat rheumatoid arthritis and associated hyperalgesia.
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Pharmacol. Biochem. Behav. · Oct 2011
Blockade of 5-HT7 receptors reduces tactile allodynia in the rat.
This study assessed the role of systemic and spinal 5-HT(7) receptors on rats submitted to spinal nerve injury. In addition, the 5-HT(7) receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5/L6 spinal nerve ligation. ⋯ Data suggest that spinal 5-HT(7) receptors play a pronociceptive role in neuropathic rats. Results also indicate that spinal nerve injury leads to a reduced 5-HT(7) receptors level in pain processing-related areas which may result from its nociceptive role in this model. Data suggest that selective 5-HT(7) receptor antagonists may function as analgesics in nerve injury pain states.
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Persistent pain associated with inflammatory arthritis is an aggravating factor that decreases patients' quality of life. Current therapies for joint pain have limited effectiveness and produce unwanted negative side effects. Although the involvement of substance P and its cognate tachykinin receptor, NK(1), in joint inflammation has been extensively documented through animal experiments, the development of oral tachykinin NK(1) receptor antagonists against arthritis-induced pain has been unsuccessful in humans to date. ⋯ Administration of the tachykinin NK(1) receptor antagonist WIN 51708 or GR 82334 into the affected ankle joint at day 3 following intra-articular CFA injection reduced the mechanical hyperalgesia 12 h after the tachykinin NK(1) receptor antagonist injection and their analgesic effects persisted for at least 2 days. Histological examinations revealed that intra-articular WIN 51708 reduced the CFA-induced destructive changes in the cartilage. These findings suggest that intra-articular injection of tachykinin NK(1) receptor antagonists is a promising strategy for relieving the hyperalgesia that occurs in inflammatory arthritis.
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Pharmacol. Biochem. Behav. · Oct 2011
Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice.
Combinations of analgesics from different classes are commonly used in the management of chronic pain. The goal is to enhance pain relief together with the reduction of side effects. The present study was undertaken to examine the anti-allodynic synergy resulting from the combination of WIN 55,212-2, a cannabinoid CB1 receptor agonist, and JTC-801, a nociceptin/orphanin FQ receptor antagonist, on neuropathic pain. ⋯ Both WIN 55,212-2 and JTC-801 produced dose-dependent mechanical and cold anti-allodynic effects. As shown by isobolographic analysis, WIN 55,212-2/JTC-801 combinations interacted synergistically at all three ratios studied in the mechanical allodynia assay. In conclusion, co-administration of a cannabinoid with a nociceptin/orphanin FQ receptor antagonist resulted in a synergistic interaction, which may have utility in the pharmacological treatment of neuropathic pain.