Analgesia produced by low doses of the opiate antagonist naloxone in arthritic rats is reduced in morphine-tolerant animals

Kayser, V.; Besson, J. M.; Guilbaud, G.

doi:10.1016/0006-8993(86)90807-3

Cited by 36 publications

(10 citation statements)

References 26 publications

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“…Indeed, the blockade, at the spinal level (i.t. administration), of all opioid receptors by a high dose of naloxone (Chen and Pan, 2006;Christensen and Kayser, 2000;Kayser et al, 1986;Tejwani and Rattan, 2002) or of GABA B R by phaclofen (Brouillette and Couture, 2002;Gwak et al, 2006) did not modify E-55888-induced anti-hyperalgesic effects ( Fig. 8A and B).…”

Section: Discussionmentioning

confidence: 73%

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GABA, but not opioids, mediates the anti-hyperalgesic effects of 5-HT7 receptor activation in rats suffering from neuropathic pain

et al. 2012

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Section: Discussionmentioning

confidence: 73%

“…The doses selected for naloxone (1 mg/kg s.c. and 10 mg i.t.) have previously been reported to block completely m, d and k opioidergic receptors (Chen and Pan, 2006;Christensen and Kayser, 2000;Kayser et al, 1986;Tejwani and Rattan, 2002). For bicuculline, we determined the maximal i.v.…”

Section: Acute Treatmentsmentioning

confidence: 94%

GABA, but not opioids, mediates the anti-hyperalgesic effects of 5-HT7 receptor activation in rats suffering from neuropathic pain

et al. 2012

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“…However, when tested by itself over a broad dose range (3 to 3000 µg/kg, iv) the naloxone produces a biphasic dose response in which analgesia occurred at low doses (3-10 µg/kg, iv) and hyperalgesia at higher doses (1000 to 3000 µg/kg, iv) in the arthritic rat model (Kayser and Guilbaud, 1981). If the rats are made morphine tolerant the biphasic response disappears, with only the hyperalgesic effect remaining Kayser et al, 1986).…”

Section: Opiates and Arthritic Painmentioning

confidence: 93%

Pain and U-Shaped Dose Responses: Occurrence, Mechanisms, and Clinical Implications

Calabrese

2008

Critical Reviews in Toxicology

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This article assesses pain within the context of the dose response. A substantial number of studies indicate that the dose response for pain-related endpoints is commonly biphasic, being independent of the type of biological model employed, endpoint measured, or agent tested. The quantitative features of the dose response are also remarkably consistent regardless of the receptor pathway that mediates the nociceptive response, indicating a likely downstream message convergence. These findings have important implications for drug discovery, development, and clinical evaluation.

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“…9 and 10). Similarly, low doses of NLX induce analgesia in normal and especially in arthritic rats, whereas only high doses elicit hyperalgesia (11)(12)(13)(14)(15)(16)(17). "Paradoxical" analgesia is also induced in rats by a brief series of daily injections of NLX or naltrexone (NTX) (18-21).…”

mentioning

confidence: 99%

“…Selective blockade of tonic excitatory, but not inhibitory, opioid receptor-mediated activity by NLX or NTX provides a simple mechanism that may underlie the paradoxical analgesia induced by these opioid antagonists, especially at low doses, in humans (1-3) and animals (4, 8-15, 18-21, 23-27). In adult rats subjected to persistent pain related to arthritic inflammation (13,14) or to peripheral neuropathy (62), single injections of 3-10 ,tg of NLX per kg (i.v.) elicited a "significant paradoxical antinociceptive effect," which has been more difficult to detect in normal adult animals (see, however, ref.…”

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confidence: 99%

Ultra-low concentrations of naloxone selectively antagonize excitatory effects of morphine on sensory neurons, thereby increasing its antinociceptive potency and attenuating tolerance/dependence during chronic cotreatment.

Crain

Shen

1995

Proc. Natl. Acad. Sci. U.S.A.

191

118

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Ultra-low picomolar concentrations of the opioid antagonists naloxone (NLX) and naltrexone (NIX) have remarkably potent antagonist actions on excitatory opioid receptor functions in mouse dorsal root ganglion (DRG) neurons, whereas higher nanomolar concentrations antagonize excitatory and inhibitory opioid functions. Pretreatment of naive nociceptive types of DRG neurons with picomolar concentrations of either antagonist blocks excitatory prolongation of the Ca2+-dependent component of the action potential duration (APD) elicited by picomolar-nanomolar morphine and unmasks inhibitory APD shortening. The present study provides a cellular mechanism to account for previous reports that low doses ofNLX and NTX paradoxically enhance, instead of attenuate, the analgesic effects of morphine and other opioid agonists. Furthermore, chronic cotreatment of DRG neurons with micromolar morphine plus picomolar NLX or NTX prevents the development of (i) tolerance to the inhibitory APD-shortening effects of high concentrations of morphine and (ii) supersensitivity to the excitatory APD-prolonging effects of nanomolar NLX as well as of ultra-low (femtomolar-picomolar) concentrations of morphine and other opioid agonists. These in vitro studies suggested that ultra-low doses of NLX or NTX that selectively block the excitatory effects of morphine may not only enhance the analgesic potency of morphine and other bimodally acting opioid agonists but also markedly attenuate their dependence liability.Subsequent correlative studies have now demonstrated that cotreatment of mice with morphine plus ultra-low-dose NTX does, in fact, enhance the antinociceptive potency of morphine in tail-flick assays and attenuate development ofwithdrawal symptoms in chronic, as well as acute, physical dependence assays.Many clinical reports have noted the unexpected and paradoxical observation that administration of low doses (<30 ,ug/kg) of the opioid antagonist naloxone (NLX) results in analgesia or enhances, rather than attenuates, the analgesic effects of morphine or other opioid agonists (refs. 1-8; see reviews in refs. 9 and 10). Similarly, low doses of NLX induce analgesia in normal and especially in arthritic rats, whereas only high doses elicit hyperalgesia (11)(12)(13)(14)(15)(16)(17). "Paradoxical" analgesia is also induced in rats by a brief series of daily injections of NLX or naltrexone (NTX) (18-21). The mechanism underlying NLX-induced analgesia and NLX enhancement of morphine-induced analgesia is unknown, although some studies have suggested that low-dose NLX may selectively block a putative opioid system that is antagonistic to analgesia (9, 10) or an endogenous dynorphin "antianalgesic system" (22). NLX may also elicit analgesia by blocking specific K opioid-mediated hyperalgesic systems in the central nervous system (ref. 23; see also refs. 24-27).Electrophysiologic studies of opioid effects on nociceptive types of dorsal root ganglion (DRG) neurons in culture have led us to propose that just as Gi/G.-coupled inhibitory opioid...

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Analgesia produced by low doses of the opiate antagonist naloxone in arthritic rats is reduced in morphine-tolerant animals

Cited by 36 publications

References 26 publications

GABA, but not opioids, mediates the anti-hyperalgesic effects of 5-HT7 receptor activation in rats suffering from neuropathic pain

GABA, but not opioids, mediates the anti-hyperalgesic effects of 5-HT7 receptor activation in rats suffering from neuropathic pain

Pain and U-Shaped Dose Responses: Occurrence, Mechanisms, and Clinical Implications

Ultra-low concentrations of naloxone selectively antagonize excitatory effects of morphine on sensory neurons, thereby increasing its antinociceptive potency and attenuating tolerance/dependence during chronic cotreatment.

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