Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate pre-synaptic influence of the descending noradrenergic system on the primary afferents containing substance P (SP), effects of noradrenergic manipulations on the in situ release of immunoreactive SP (iSP) from the dorsal horn were examined in the thalamic rabbit. Local application of noradrenaline (10 microM) to the dorsal horn produced complete inhibition of the noxious mechanical stimuli-evoked release of iSP. This effect was reversed by yohimbine (the more selective alpha 2-blocker, 10 microM) and partially antagonized by prazosin (the more selective alpha 1-blocker, 10 microM). The resting release of iSP was not affected by noradrenaline. The noxious mechanical stimuli-evoked release of iSP was significantly increased by acute spinal transection and local application of yohimbine (10 microM) alone to the dorsal horn. Prazosin (10 microM) slightly increased the evoked iSP release, and a beta-blocker metoprolol did not affect it. These results suggest that the nociceptive primary afferents containing SP are tonically inhibited by the descending noradrenergic system linked to alpha-adrenoceptors, and that such alpha-adrenoceptors located on the primary afferent terminals may be one of the sites of action of noradrenaline spinal analgesia. In contrast to the evoked iSP release, the resting iSP release was increased only by acute spinal transection and not by yohimbine, prazosin and metoprolol. All these observations suggest that tonic inhibition in propriospinal neurons containing SP is mediated by a non-noradrenergic system.
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PMID:Noradrenergic inhibition of the release of substance P from the primary afferents in the rabbit spinal dorsal horn. 241 95

Rapid development of tolerance and dependence limits the usefulness of morphine in long-term treatment. We examined the effects of clonidine (alpha(2)-adrenoceptor agonist) and prazosin (alpha(1)-adrenoceptor antagonist) on morphine analgesia, tolerance and withdrawal. Morphine tolerance was induced using a 3-day cumulative twice-daily dosing regimen with s.c. doses up to 120 mg/kg. Tolerance was assessed on day 4, as loss of the antinociceptive effect of a test dose of morphine (5 mg/kg). After 10 h, morphine withdrawal was precipitated with naloxone (1 mg/kg). Prazosin had no analgesic effect alone but dose-dependently potentiated morphine analgesia in morphine-naive mice. Another alpha(1)-adrenoceptor antagonist, corynanthine, had similar effects. Prazosin also increased the analgesic potency of the morphine test dose in morphine-tolerant mice. Naloxone-precipitated vertical jumping was not affected, but weight loss was reduced by prazosin. Acutely administered clonidine potentiated morphine analgesia and alleviated opioid withdrawal signs, as expected. We conclude that in addition to the already established involvement of alpha(2)-adrenoceptors in opioid actions, also alpha(1)-adrenoceptors have significant modulatory role in opioid analgesia and withdrawal.
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PMID:Influence of prazosin and clonidine on morphine analgesia, tolerance and withdrawal in mice. 1255 72

Alpha(2)-adrenoceptor agonists potentiate opioid analgesia and alleviate opioid withdrawal. The effects of two alpha(2)-adrenoceptor agonists, clonidine (2 mg/kg) and dexmedetomidine (20 and 100 microg/kg), and the alpha(1)-adrenoceptor antagonist prazosin (0.5 mg/kg) were tested on morphine analgesia, tolerance, and withdrawal in wild-type and alpha(2A)-adrenoceptor knock-out (KO) mice. Analgesia and tolerance were assessed with the tail-flick test. Withdrawal was precipitated with naloxone. Prazosin potentiated morphine analgesia equally in both genotypes. Clonidine and dexmedetomidine had no analgesic effects in alpha(2A)-adrenoceptor KO mice, but morphine analgesia and tolerance were similar in both genotypes. Alpha(2A)-Adrenoceptor KO mice exhibited 70% fewer naloxone-precipitated jumps than wild-type mice; weight loss was similar in both genotypes. The alpha(2)-adrenoceptor agonists reduced opioid withdrawal signs only in wild-type mice. We conclude that alpha(2A)-adrenoceptors are not directly involved in morphine analgesia and tolerance, and not critical for potentiation of morphine analgesia by prazosin, but that alpha(2A)-adrenoceptors modulate the expression of opioid withdrawal signs in mice.
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PMID:The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice. 1530 1