Articles: hyperalgesia.
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The vanilloid TRPV1 receptor, present on primary afferent fibres, is activated by noxious heat, low pH and endogenous vanilloids. Changes in the function or distribution of TRPV1 receptors may play an important role in pain induced by inflammation or neuropathy. The aim of the present study was to evaluate the role of peripheral TRPV1 receptors in thermal nociception in rat models of inflammatory and neuropathic pain. ⋯ The higher dose of IRTX (0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked responses in both inflamed and naïve rats. In sham-operated and SNL rats, IRTX (0.004 and 0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked, but had no effect on mechanically evoked responses of WDR neurons. These data support the role of peripheral TRPV1 receptors in noxious thermal transmission in naïve, inflamed and neuropathic rats, and suggest that there is an increased functional contribution of peripheral TRPV1 receptors following acute inflammation.
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Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain, suggesting the presence of hyperalgesia. It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations. In the former case, hyperalgesia should occur when intensity of non-painful sensations is still low. The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways. ⋯ Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures. Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations. These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity.
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Abnormal spontaneous firing is well described in axotomized sensory neurons and likely contributes to nerve injury-induced pain. The hyperpolarization-activated current I(h) initiates spontaneous, rhythmic depolarization in the sinoatrial node and central neurons. This study was undertaken to investigate the possible contribution of I(h) to primary afferent ectopic discharge and pain behavior in nerve-injured rats. Nerve injury was produced by tight ligation of lumbar spinal nerves (L5/6). Two weeks later, rats showed marked mechanical allodynia. Withdrawal thresholds were measured before and after administration of saline or the specific I(h) antagonist ZD7288 (1, 3, or 10 mg/kg, intraperitoneally). ZD7288 dose-dependently reversed mechanical allodynia. In a second experiment, we performed both in vivo and in vitro extracellular single unit recordings from teased dorsal root fascicles. Intravenous infusion (2.5 or 5 mg/kg) of ZD7288 during a period of 10 minutes significantly blocked ectopic discharges in vivo. Perfusion (25 to 100 mumol/L) of ZD7288 for 5 minutes in vitro almost completely blocked ectopic discharges from large myelinated fibers (Abeta) while partially suppressing ectopic discharge from thinly myelinated fibers (Adelta). We conclude from these data that in axotomized sensory neurons, a ZD7288-sensitive current contributes to spontaneous discharges in myelinated fibers. Thus, I(h) might substantially contribute to the pathophysiology of nerve injury-related neuropathic pain. ⋯ The current study investigated the mechanism of abnormal spontaneous discharges (ectopic discharges) from axotomized sensory afferents. Ectopic discharges are a main driving source of nerve injury-induced neuropathic pain. Understanding the mechanism of ectopic discharges and identifying how to control them will be useful toward developing new therapies.
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While it is well established that acute stress can produce antinociception, a phenomenon referred to as stress-induced analgesia, repeated exposure to stress can have the opposite effect. Since, chronic pain syndromes, such as fibromyalgia and rheumatoid arthritis, may be triggered and/or exacerbated by chronic stress, we have evaluated the effect of repeated stress on mechanical nociceptive threshold and inflammatory hyperalgesia. Using the Randall-Selitto paw pressure test to quantify nociceptive threshold in the rat, we found that repeated non-habituating sound stress enhanced the mechanical hyperalgesia induced by the potent inflammatory mediator, bradykinin, which, in normal rats, produces hyperalgesia indirectly by stimulating the release of prostaglandin E2 from sympathetic nerve terminals. ⋯ In addition, implants of epinephrine restored bradykinin-hyperalgesia in sympathectomized non-stressed rats, lending further support to the suggestion that increased plasma levels of epinephrine can sensitize primary afferents to bradykinin. These results suggest that stress-induced enhancement of inflammatory hyperalgesia is associated with a change in mechanism by which bradykinin induces hyperalgesia, from being sympathetically mediated to being sympathetically independent. This sympathetic-independent enhancement of mechanical hyperalgesia is mediated by the stress-induced release of epinephrine from the adrenal medulla.
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Opioids, intended to abolish pain, can unexpectedly produce hyperalgesia, particularly during rapid opioid escalation. Opioid switching could be a therapeutic option in a condition of opioid-induced tolerance or hyperalgesia, but conversion ratios between opioids are difficult to apply in this context and require strict surveillance and expertise. This situation is challenging, because the rapid escalation of opioid doses, possibly due to the development of opioid-induced tolerance, can cause hyperalgesia. ⋯ The authors present a case report in which switching from fentanyl to methadone was effective in a patient who developed hyperalgesia as a consequence of a rapid opioid escalation. Regardless of the expected clinical improvement of opioid switching using lower doses of the second opioid, the final dose of the second opioid was exaggeratedly low, probably as a consequence of the disappearance of hyperalgesia induced by the first opioid. The results of this case and others like it may help practitioners develop a meaningful approach during opioid escalation, possibly anticipating the need for opioid switching or other alternative measures for patients with uncontrolled cancer pain.