Articles: hyperalgesia.
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Anesthesia and analgesia · Aug 2009
Long-term pain vulnerability after surgery in rats: prevention by nefopam, an analgesic with antihyperalgesic properties.
Tissue damage associated with surgery often produces peripheral and central sensitization that may outlast the stimuli, leading to exaggerated postoperative pain. Paradoxically, the use of opioid analgesia, which is essential for surgical pain management may induce pain sensitization leading to enhanced postoperative pain and an increased risk of developing chronic pain. We studied whether a surgical incision in the rat hindpaw may favor the development of long-term pain vulnerability by estimating hyperalgesia induced by an inflammatory stimulation of the unlesioned contralateral hindpaw 3 wk later. We also evaluated the ability of nefopam, an analgesic drug commonly used in postoperative pain management, to prevent not only exaggerated postoperative pain but also long-term pain vulnerability. The efficacy of morphine was assessed 1 day after surgical incision. ⋯ Given preemptively, nefopam may be effective at improving postoperative pain management and at reducing the risk of developing postoperative chronic pain, because the drug has both analgesic and antihyperalgesic properties.
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Spinal long-term potentiation (LTP) elicited by noxious stimulation enhances the responsiveness of dorsal horn nociceptive neurons to their normal input, and may represent a key mechanism of central sensitization by which acute pain could turn into a chronic pain state. This study investigated the electrophysiological and behavioral consequences of the interactions between LTP and descending oxytocinergic antinociceptive mechanisms mediated by the hypothalamic paraventricular nucleus (PVN). ⋯ In a behavioral model developed to study the effects of spinal LTP on mechanical withdrawal thresholds in freely moving rats, the long-lasting LTP-mediated mechanical hyperalgesia was transiently interrupted or prevented by either PVN stimulation or intrathecal OT. LTP mediates long-lasting pain hypersensitivity that is strongly modulated by endogenous hypothalamic oxytocinergic descending controls.
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Basic Clin. Pharmacol. Toxicol. · Aug 2009
Randomized Controlled TrialEvoked human oesophageal hyperalgesia: a potential tool for analgesic evaluation?
Hypersensitivity is a common finding in visceral disorders. Therefore, in the development and testing of analgesics for the treatment of visceral pain, it is important to establish an experimental pain model of visceral hypersensitivity. Such a model will mimic the clinical situation to a higher degree than pain models where the receptors and peripheral afferents are briefly activated as with, for example, electrical, thermal, and mechanical stimulations. ⋯ Acid+capsaicin perfusion induced 56% reduction of the pain threshold to heat (P = 0.04), 19% reduction of the pain threshold to electrical stimuli (P < 0.001), 78% increase of the referred pain areas to mechanical stimulation (P < 0.001) and 52% increase of the referred pain areas to electrical stimulus (P = 0.045). All volunteers were sensitised to one or more modalities by acid+capsaicin. The model was able to evoke consistent hyperalgesia and may be useful in future pharmacological studies.
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The involvement of TRPV1 and TRPA1 in mediating craniofacial muscle nociception and mechanical hyperalgesia was investigated in male Sprague-Dawley rats. First, we confirmed the expression of TRPV1 in masseter afferents in rat trigeminal ganglia (TG), and provided new data that TRPA1 is also expressed in primary afferents innervating masticatory muscles in double-labeling immunohistochemistry experiments. We then examined whether the activation of each TRP channel in the masseter muscle evokes acute nocifensive responses and leads to the development of masseter hypersensitivity to mechanical stimulation using the behavioral models that have been specifically designed and validated for the craniofacial system. ⋯ Similarly, pretreatment of the muscle with a selective TRPA1 antagonist, AP18, significantly blocked the MO-induced muscle nociception and mechanical hyperalgesia. We confirmed these data with another set of selective antagonist for TRPV1 and TRPA1, AMG9810 and HC030031, respectively. Collectively, these results provide compelling evidence that TRPV1 and TRPA1 can functionally contribute to muscle nociception and hyperalgesia, and suggest that TRP channels expressed in muscle afferents can engage in the development of pathologic muscle pain conditions.
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Although morphine is a potent antinociceptive agent, its chronic use developed tolerance in neuropathic pain (NP). Furthermore, opioid antagonist naloxone attenuated the antinociceptive effect of neuropeptide Y (NPY). The present study investigated the role of NPY and NPY Y1/Y5 receptors in acute and chronic actions of morphine in neuropathic rats using thermal paw withdrawal test and immunocytochemistry. ⋯ NPY-immunoreactivity profile of LC remained unchanged in all the morphine treatment conditions. Furthermore, removal of sciatic nerve ligation reversed the effects of NP, increased pain threshold and restored NPY-ir fiber population in VLPAG. NPY, perhaps acting via Y1/Y5 receptors, might profoundly influence the processing of NP information and interact with the endogenous opioid system primarily within the framework of the VLPAG.