Articles: hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Peripheral opioid analgesia in experimental human pain models.
This placebo-controlled, double-blind crossover study assessed whether exclusive activation of peripheral opioid receptors results in significant pain reduction. To achieve opioid activity restricted to the periphery, we used a short-term (2 h) low dose infusion of morphine-6-beta-glucuronide (M6G) because M6G does not pass the blood-brain barrier during this time in amounts sufficient to induce CNS effects. The lack of central opioid effects of M6G was confirmed by a lack of change of the pupil size and absence of other opioid-related CNS effects. ⋯ Subcutaneous tissue concentrations of M6G and morphine as assessed with microdialysis were about half those of the respective plasma concentrations. The results of the study indicate that M6G has antihyperalgesic effects in inflammatory pain through activation of peripheral opioid receptors. Since this occurs at concentrations that do not cause central opioid effects, M6G might be useful as a peripheral opioid analgesic.
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Referred muscle pain, resulting from algogenic conditions in viscera or other deep somatic structures (another muscle, a joint), is most often accompanied by secondary hyperalgesia and trophic changes (hypotrophy). Referred pain/ hyperalgesia from viscera is partly due to central sensitisation of viscero-somatic convergent neurons (triggered by the massive afferent visceral barrage) but also probably results from a reflex arc activation (the visceral input triggers reflex muscle contraction in turn responsible for sensitisation of muscle nociceptors). Referred pain/hyperalgesia from deep somatic structures is not explained by the mechanism of central sensitisation of convergent neurons in its original form, since there is little,convergence from deep tissues in the dorsal horn neurons. It has been proposed that these connections, not present from the beginning, are opened by nociceptive input from skeletal muscle, and that referral to myotomes outside the lesion results from the spread of central sensitisation to adjacent spinal segments.
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Arthritis and rheumatism · May 2003
Clinical TrialNeurophysiologic evidence for a central sensitization in patients with fibromyalgia.
To determine whether abnormalities of peripheral and central nociceptive sensory input processing exist outside areas of spontaneous pain in patients with fibromyalgia (FM) as compared with controls, by using quantitative sensory testing (QST) and a neurophysiologic paradigm independent from subjective reports. ⋯ Our results strongly, although indirectly, point to a state of central hyperexcitability of the nociceptive system in patients with FM. The NFR can be used to assess central allodynia in FM. It may also help discriminate patients who may benefit from use of centrally acting analgesics.
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Inflammation of a peripheral nerve (neuritis) causes mechanical and thermal hyperalgesia in the region in which the inflamed nerve innervates. We investigated whether peripherally applied norepinephrine (NE) would exacerbate mechanical hyperalgesia in rats with neuritis. After inflammation of the left L5 spinal nerve with complete Freund's adjuvant, the foot withdrawal thresholds to mechanical stimuli applied to the affected hind paw (mechanical thresholds) were decreased significantly, indicating the development of mechanical hyperalgesia. ⋯ The effect of NE on mechanical hyperalgesia was mediated by both peripheral alpha(1)- and alpha(2)-adrenoceptors. Immunohistochemical study of the previously inflamed nerve showed that proinflammatory cytokine tumor necrosis factor immunoreactivity was significantly higher in the rats showing adrenergic sensitivity compared to rats without adrenergic sensitivity. The data thus suggest that peripheral NE, when released in an excessive amount from the sympathetic nervous system, might play an important role in the aggravation of pain in neuritis.
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Comparative Study
Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome.
We have previously shown that irritable bowel syndrome (IBS) patients have both visceral and cutaneous hyperalgesia. The neural mechanisms of these forms of hyperalgesia were further characterized by comparing cortical processing of both rectal distension (35, 55mmHg) and cutaneous heat nociceptive stimuli (foot immersion in 45 and 47 degrees C water bath) in IBS patients and in a group of healthy age/sex-matched controls. Our approach relied on functional magnetic resonance imaging neuroimaging analyses in which brain activation in age/sex-matched control subjects was subtracted from that found in IBS patients. ⋯ This was found to be the case not only for visceral hyperalgesia but also for cutaneous heat hyperalgesia, a likely form of secondary hyperalgesia. Furthermore, visceral and heat hyperalgesia were accompanied by increased neural activity within the same brain structures. These results support the hypothesis that visceral and cutaneous hyperalgesia in IBS patients is related to increased afferent processing in pathways ascending to the brain rather than to selectively increased activity at higher cortical levels (e.g. limbic and frontal cortical areas).