Articles: hyperalgesia.
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Using a model of visceral nociception, we examined whether cholecystokinin (CCK) acts as an anti-opioid peptide in the rat rostral ventromedial medulla (RVM). Because such interaction may be affected by inflammation, rats with and without inflamed colons were studied. The visceromotor response to noxious colorectal distension (CRD), quantified electromyographically, was recorded before and after intra-RVM administration of CCK, CCK receptor antagonists, and morphine. ⋯ Intra-RVM CCK-8 peptide enhanced responses to CRD in intracolonic vehicle-treated, but not TNBS-treated rats. Intra-RVM naloxone was without effect in intracolonic vehicle-or TNBS-treated rats, suggesting an absence of tonic opioid activity in RVM. These results document a CCK-opioid interaction in RVM, suggesting that colon inflammation leads to tonic activity at CCK(B) receptors in RVM.
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The contribution for the development of secondary mechanical hyperalgesia by peripheral mechanisms has not been fully elucidated. We have reevaluated the effects of local anesthetics on electrically evoked flare reaction and mechanical hyperalgesia in human skin. We applied 2% lidocaine via intradermal microdialysis fibers at a length of 10 cm for 110 min to the volar forearm to establish a narrow and stable "anesthetic strip." After 60 min of lidocaine perfusion, transdermal electrical stimulation (1 Hz, 50 mA) was applied at a distance of 1 cm from the microdialysis fibers for 30 min. ⋯ In contrast, allodynia (7.4 +/- 0.7 and 8.6 +/- 0.9 cm) and punctate hyperalgesia (7.6 +/- 0.7 and 8.6 +/- 0.9 cm) developed symmetrically on both sides of the anesthetic strip. Allodynia subsided 4 min after the end of the electrical stimulation. We conclude that the development of allodynia and punctate hyperalgesia in human skin is centrally mediated, whereas the axon reflex vasodilation is of peripheral origin.
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1. Paeonol was tested for its anti-inflammatory and analgesic effects in a rat model of carrageenan-evoked thermal hyperalgesia. The possible mechanisms involved in these effects were also investigated. 2. ⋯ Elevated myeloperoxidase activity, an indicator of neutrophil infiltration, in carrageenan-injected paws was also dose-dependently reduced in paeonol-treated rats. 6. Our results suggest that the mechanisms by which paeonol exerts its anti-inflammatory and analgesic effects in this inflammatory model may be associated with decreased production of proinflammatory cytokines, NO and PGE(2) and increased production of IL-10, an anti-inflammatory cytokine, in carrageenan-injected rat paws. In addition, attenuation of the elevated iNOS and COX-2 protein expression as well as neutrophil infiltration in carrageenan-injected paws may also be involved in the beneficial effects of paeonol.
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Anesthesia and analgesia · Jul 2003
Peripheral antihyperalgesic and analgesic actions of ketamine and amitriptyline in a model of mild thermal injury in the rat.
In this study, we examined antihyperalgesic and analgesic actions after local peripheral administration of ketamine and amitriptyline in a rat model of mild thermal injury. Exposure of the hindpaw to 52 degrees C for 45 s under anesthesia produced a subsequent thermal hyperalgesia lasting at least 2 h. The local peripheral administration of ketamine (100-1000 nmol) 15 min before the thermal injury produced an antihyperalgesic effect when injected into the ipsilateral paw, whereas amitriptyline produced both antihyperalgesic (300 nmol) and analgesic (1000 nmol) effects. Administered after the thermal injury, ketamine had no effect, whereas amitriptyline retained its analgesic but not its antihyperalgesic effect. Amitriptyline (300 and 1000 nmol) produced an analgesic action when administered into the normal nonsensitized hindpaw. Both drugs increase paw volume, particularly at larger doses; biogenic amines are not involved in the action of amitriptyline, as was shown previously for ketamine. These results indicate that (a) ketamine produces antihyperalgesia, but not analgesia, when administered locally with a mild thermal injury model; (b) amitriptyline produces both antihyperalgesia and analgesia when administered locally; and (c) the increase in paw volume produced by these drugs occurs by different mechanisms. ⋯ This study examines the pain-relieving properties of the local peripheral administration of ketamine and amitriptyline, two drugs in current clinical use, in a thermal injury model of hyperalgesia and demonstrates both antihyperalgesic and analgesic properties. These observations provide support for their potential use as local (e.g., topical) analgesics.
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Animals made ill by intraperitoneal injection with toxins, such as lithium chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive neurocircuitry and spinal pharmacology that underlie these effects bear the same features as those that mediate analgesic tolerance to morphine [Neurosci. Biobehav. ⋯ Furthermore, these effects occurred in the absence of detectable hyperalgesia indicating that illness-induced tolerance was not the result of an increase in pain sensitivity offsetting analgesia. Finally, rats tested in a context associated with LiCl demonstrated less morphine analgesia than rats tested in a context not associated with LiCl or rats naive to LiCl suggesting that illness activates descending mechanisms that antagonize analgesia rather than simply desensitizing opioid receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents also activate endogenous antianalgesic mechanisms.