Articles: hyperalgesia.
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Opiates are currently the mainstay for treatment of moderate to severe pain. However, prolonged administration of opiates has been reported to elicit hyperalgesia in animals, and examples of opiate-induced hyperalgesia have been reported in humans as well. Despite the potential clinical significance of such opiate-induced actions, the mechanisms of opiate-induced hypersensitivity remain unknown. The transient receptor potential vanilloid1 (TRPV1) receptor, a molecular sensor of noxious heat, acts as an integrator of multiple forms of noxious stimuli and plays an important role in the development of inflammation-induced hyperalgesia. Because animals treated with opiates show thermal hyperalgesia, we examined the possible role of TRPV1 receptors in the development of morphine-induced hyperalgesia using TRPV1 wild-type (WT) and knock-out (KO) mice and with administration of a TRPV1 antagonist in mice and rats. Administration of morphine by subcutaneous implantation of morphine pellets elicited both thermal and tactile hypersensitivity in TRPV1 WT mice but not in TRPV1 KO mice. Moreover, oral administration of a TRPV1 antagonist reversed both thermal and tactile hypersensitivity induced by sustained morphine administration in mice and rats. Immunohistochemical analyses indicate that sustained morphine administration modestly increases TRPV1 labeling in the dorsal root ganglia. In addition, sustained morphine increased flinching and plasma extravasation after peripheral stimulation with capsaicin, suggesting an increase in TRPV1 receptor function in the periphery in morphine-treated animals. Collectively, our data indicate that the TRPV1 receptor is an essential peripheral mechanism in expression of morphine-induced hyperalgesia. ⋯ Opioid-induced hyperalgesia possibly limits the usefulness of opioids, emphasizing the value of alternative methods of pain control. We demonstrate that TRPV1 channels play an important role in peripheral mechanisms of opioid-induced hyperalgesia. Such information may lead to the discovery of analgesics lacking such adaptations and improving treatment of chronic pain.
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This observational study aimed to determine whether pain sensitivity in patients with noncancer chronic pain, taking either methadone or morphine, is similar to patients maintained on methadone for dependence therapy, compared with a control group. Nociceptive thresholds were measured on a single occasion with von Frey hairs, electrical stimulation, and cold pressor tests. In all subjects receiving methadone or morphine, nociceptive testing occurred just before a scheduled dose. Cold pressor tolerance values in patients with noncancer, chronic pain, treated with morphine and methadone, were 18.1 +/- 2.6 seconds (mean +/- SEM) and 19.7 +/- 2.3 seconds, respectively; in methadone-maintained subjects it was 18.9 +/- 1.9 seconds, with all values being significantly (P < .05) lower than opioid-naïve subjects (30.7 +/- 3.9 seconds). These results indicate that patients with chronic pain managed with opioids and methadone-maintained subjects are hyperalgesic when assessed by the cold pressor test but not by the electrical stimulation test. None of the groups exhibited allodynia as measured using the von Frey hairs. These results add to the growing body of evidence that chronic opioid exposure increases sensitivity to some types of pain. They also demonstrate that in humans, this hyperalgesia is not associated with allodynia. ⋯ This article presents an observational study whereby the pain sensitivity of patients with chronic pain managed with opioids and opioid-maintained patients were compared with opioid-naïve patients. The results suggest that opioid use may contribute to an increase in the sensitivity to certain pain experimental stimuli.
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The effect of the alpha(1)-adrenoceptor agonist phenylephrine on sensitivity to heat was investigated at three sites of mild burn injury in the cutaneous forearm of 19 healthy participants. Two of the sites were pre-treated with the alpha(1)-antagonist terazosin, to determine whether the effect of phenylephrine was mediated by alpha(1)-adrenoceptors. Terazosin was administered before the burn injury at one site, and after the burn injury at the other site. ⋯ However, neither alpha(2)-adrenoceptor stimulation nor blockade affected sensitivity to heat in the mildly burnt skin. These findings suggest that stimulation of cutaneous alpha(1)-adrenoceptors increased the excitability of heat-sensitized nociceptive afferents. As terazosin was more effective when administered in burnt skin, an inflammatory response induced by the burn injury may have facilitated access of adrenergic agents to alpha(1)-adrenoceptors.
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Distortions of the body image have been repeatedly reported for various clinical conditions, but direct experimental analyses of the perceptual changes involved are still scarce. In addition, most experimental studies rely on cerebral activation patterns to assess neuroplastic changes in central representation, although the relationship between cerebral topography and the topology of the perceptual space is not clear. This study examines whether the direct psychophysical mapping approach we introduced recently (Trojan et al., Brain Res 2006;1120:106-113) is capable of tracking perceptual distortions in the somatotopic representation of heat-pain stimuli. ⋯ We found that the topology and metrics of the somatotopic representation were well preserved in the second session, but that the perceptual map was compressed to a smaller range in 9 out of 11 participants. By providing dimensional measures of perceptual representations, perceptual maps constitute an independent, genuinely psychological complement to the topography of cortical activations measured with neuroimaging methods. In addition, we expect them to be useful in diagnosing pathological changes in body perception accompanying chronic pain and other disorders.