Articles: hyperalgesia.
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Chronic muscle pain is common and often difficult to treat. In this study, we further characterize a model of chronic muscle pain induced by repeated intramuscular injection of acidic saline. Two injections of acid into muscle separated by 5 days result in secondary mechanical hyperalgesia that lasts for up to 4 weeks. ⋯ The second intramuscular injection evoked a calcium-dependent increase in both spinal glutamate and aspartate concentrations. Glutamate concentrations within the dorsal horn were also increased 1 week after the second acid injection. Our data suggest increased release of spinal EAAs in the dorsal horn contributes to the development and maintenance of hyperalgesia.
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Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain (cold allodynia). To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain. ⋯ The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms.
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Proc. Natl. Acad. Sci. U.S.A. · Dec 2005
Randomized Controlled Trial Comparative StudyPharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.
Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. ⋯ We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.
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Anesthesia and analgesia · Dec 2005
Spinal L-type calcium channel blockade abolishes opioid-induced sensory hypersensitivity and antinociceptive tolerance.
Recent studies have suggested that prolonged exposure to morphine results in the development of paradoxical, abnormal enhanced pain. It has also been suggested that this enhanced pain state may be interpreted as antinociceptive tolerance. Although the precise mechanisms that drive opioid-induced abnormal pain are not well known, considerable evidence suggests that this state may be supported by enhanced, stimulus-evoked excitatory transmission. ⋯ These hypersensitivities were prevented by the coadministration of the putative selective L-type calcium channel blocker amlodipine. Moreover, mice receiving morphine for 8 days demonstrated a significant rightward shift of the morphine antinociceptive dose-response curve, indicative of antinociceptive tolerance, whereas those that also received amlodipine along with morphine did not demonstrate tolerance. These results suggest that blockade of the L-type calcium channels with amlodipine prevented opioid-induced hyperalgesia and the expression of antinociceptive tolerance to spinal morphine, presumably by reducing stimulus-induced excitatory neurotransmitter release.
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The present studies were conducted to examine functional consequences of postnatal chronic inflammation, initiated during a critical developmental period, on capsaicin-evoked hyperalgesia and neuronal activation in adulthood. Rats received a unilateral intraplantar injection of complete Freund's adjuvant (CFA; diluted 2:1 in saline) on postnatal day 0 (P0-CFA) or 14 (P14-CFA). Separate groups received an equivalent volume of saline on P0 (P0-vehicle) or were untreated (P0-untreated). Increases in capsaicin-evoked thermal and mechanical hyperalgesia and allodynia were observed in adult P0-CFA-treated rats relative to control conditions. By contrast, this enhancement was absent in P14-CFA-treated rats, suggesting that the developmental period differentially affects the appearance of the observed behavioral phenotype. Capsaicin-evoked nocifensive behavior was also lower in P14-CFA-treated rats relative to P0-CFA-treated rats. Capsaicin-evoked Fos protein expression was increased in the superficial and neck regions of the dorsal horn of adult P0-CFA-treated rats relative to P0-vehicle-treated rats. These changes were absent in the nucleus proprius and ventral horn. The present data are consistent with the hypothesis that neonatal chronic inflammation permanently alters sensitivity to pain in adulthood, consistent with modulation of primary afferent activation and central sensitization in response to a subsequent nociceptive challenge in adulthood. ⋯ Chronic inflammation during development can induce profound alterations in sensory processing later in life. Here we show that long-term inflammation initiated at critical developmental stages sensitizes both behavioral and neuronal responses to nociceptor stimulation in adulthood. An ongoing sensitization of the spinal cord is induced by the postnatal inflammatory insult.