Tolerance to the antinociceptive effects of peripherally administered opioids

Hernández, Lissette Pérez; Romero, Asunción; Almela, Pilar; Garcı́a-Nogales, Paula; Laorden, M. Luisa; Puig, Margarita M.

doi:10.1016/j.brainres.2008.10.065

Cited by 18 publications

(18 citation statements)

References 38 publications

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“…Although the current study supports peripheral opioid tolerance [2,15,16,22,28], a previous finding showed that acute tolerance did not develop to the inhibitory effect of loperamide on herpetic allodynia in mice [30]. This discrepancy between these studies may be attributable to differences in the species and animal models, which could significantly affect the peripheral opioid tolerance that results from differences in neuropathic etiology and pathophysiology.…”

Section: Discussioncontrasting

confidence: 71%

“…Opioid tolerance is generally considered to be primarily due to central nervous system (CNS) effects, and studies in animal models of inflammatory pain suggest that peripheral opioid analgesia is not associated with tolerance [38,43,51]. However, other reports suggest that the peripheral nervous system (PNS) is an important site of systemic morphine tolerance and that tolerance also develops to the antinociceptive effect of topically applied morphine [2,15,16,22,28]. Although some reports suggest that nerve injury facilitates the development of morphine tolerance [5,11,47], others indicate that acute morphine tolerance does not develop in rats with a mononeuropathy or in mice with herpes-associated neuropathic pain behavior [25,30].…”

Section: Introductionmentioning

confidence: 99%

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Tolerance develops to the antiallodynic effects of the peripherally acting opioid loperamide hydrochloride in nerve-injured rats

Yang

Perez

et al. 2013

Pain

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Peripherally acting opioids are potentially attractive drugs for the clinical management of certain chronic pain states due to the lack of centrally mediated adverse effects. However, it remains unclear whether tolerance develops to peripheral opioid analgesic effects under neuropathic pain conditions. We subjected rats to L5 spinal nerve ligation (SNL) and examined the analgesic effects of repetitive systemic and local administration of loperamide hydrochloride, a peripherally acting opioid agonist. We found that the inhibition of mechanical hypersensitivity, an important manifestation of neuropathic pain, by systemic loperamide (1.5 mg/kg subcutaneously) decreased after repetitive drug treatment (tolerance-inducing dose: 0.75 to 6.0 mg/kg subcutaneously). Similarly, repeated intraplantar injection of loperamide (150 µg/50 µL intraplantarly) and D-Ala2-MePhe4-Glyol5 enkephalin (300 µg/50 µL), a highly selective mu-opioid receptor (MOR) agonist, also resulted in decreased inhibition of mechanical hypersensitivity. Pretreatment with naltrexone hydrochloride (5 mg/kg intraperitoneally) and MK-801 (0.2 mg/kg intraperitoneally) attenuated systemic loperamide tolerance. Western blot analysis showed that repetitive systemic administration of morphine (3 mg/kg subcutaneously), but not loperamide (3 mg/kg subcutaneously) or saline, significantly increased MOR phosphorylation in the spinal cord of SNL rats. In cultured rat dorsal root ganglion neurons, loperamide dose-dependently inhibited KCl-induced increases in [Ca2+]i. However, this drug effect significantly decreased in cells pretreated with loperamide (3 µM, 72 hours). Intriguingly, in loperamide-tolerant cells, the delta-opioid receptor antagonist naltrindole restored loperamide’s inhibition of KCl-elicited [Ca2+]i increase. Our findings indicate that animals with neuropathic pain may develop acute tolerance to the antiallodynic effects of peripherally acting opioids after repetitive systemic and local drug administration.

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Section: Discussioncontrasting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Tolerance develops to the antiallodynic effects of the peripherally acting opioid loperamide hydrochloride in nerve-injured rats

Yang

Perez

et al. 2013

Pain

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“…In fact, these ligands were shown to possess significant analgesic properties in diverse pain paradigms (Bilsky et al, 1995; Chiba et al, 1996; Hosohata et al, 2000; Baker et al, 2002). Indeed, compounds activating DOPR relieve inflammation-induced thermal hyperalgesia (Desmeules et al, 1993; Stewart and Hammond, 1994; Fraser et al, 2000a; Hurley and Hammond, 2000; Qiu et al, 2000; Brandt et al, 2001a; Cahill et al, 2003; Petrillo et al, 2003; Gallantine and Meert, 2005; Gendron et al, 2007a; Le Bourdonnec et al, 2008; Gaveriaux-Ruff et al, 2008; Hernandez et al, 2009; Codd et al, 2009), neuropathic pain (Desmeules et al, 1993; Mika et al, 2001; Petrillo et al, 2003; Holdridge and Cahill, 2007; Kabli and Cahill, 2007), and cancer-related pain (Brainin-Mattos et al, 2006). As confirmed in the present study, spinal delivery of deltorphin II induces a time- and dose-dependent antihyperalgesic effect both in rats and mice (see Gendron et al, 2007b for the dose–response curves of deltorphin II in mice), an effect previously shown to be DOPR-mediated (Gendron et al, 2007b).…”

Section: Discussionmentioning

confidence: 99%

Differential noxious and motor tolerance of chronic delta opioid receptor agonists in rodents

Beaudry

Proteau-Gagné

et al. 2009

Neuroscience

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In the present study, we asked whether multiple intrathecal injections of deltorphin II, a selective delta opioid receptor (DOPR) agonist, induced DOPR tolerance in three behavioral assays. Unilateral inflammation caused by complete Freund’s adjuvant (CFA) injection into the rat or mouse hind paw (CFA model) induced thermal hyperalgesic response that was transiently and dose-dependently reduced by intrathecal administration of deltorphin II or morphine. In both rodent species, the effect of deltorphin II was not modified by a single prior administration of deltorphin II, suggesting an absence of acute tolerance in this paradigm. Repeated administration of intrathecal deltorphin II or s.c. SB-235863 (five consecutive injections over 60 h) also failed to impair the antihyperalgesic response to delta opioid receptor agonist, whereas repeated intrathecal or s.c. injections of morphine induced a significant decrease in the subsequent thermal antihyperalgesic response to morphine. In mice, deltorphin II also induced a rapid, transient motor incoordination/ ataxia-like behavior as tested with the accelerating rotarod. In contrast to the antihyperalgesic responses, tolerance to the motoric effect of deltorphin II was evident in mice previously exposed to multiple intrathecal agonist injections, but not multiple saline administrations. Using the tail flick antinociceptive test, we found that DOPR-mediated analgesia was significantly reduced by repeated exposure to deltorphin II. Altogether, these observations suggest that repeated injections of DOPR agonists induce differential tolerance effects on antihyperalgesic, antinociceptive, and motor incoordination/ataxia-like behaviors related to DOPR activation by deltorphin II. © 2009 Published by Elsevier Ltd on behalf of IBRO.

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“…Analgesic tolerance to opioid drugs is described by a reduced responsiveness to these compounds and is usually expressed by the need to use increasing doses to achieve the desired effect. In the other hand, abrupt cessation of chronic opioid use produces an intense but rarely life-threatening withdrawal syndrome in both animals and humans which is associated with physical dependence (Hernandez et al, 2009;Williams et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin

Mansouri

Khodayar

Tabatabaee

et al. 2015

Pharmacology Biochemistry and Behavior

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Tolerance to the antinociceptive effects of peripherally administered opioids

Cited by 18 publications

References 38 publications

Tolerance develops to the antiallodynic effects of the peripherally acting opioid loperamide hydrochloride in nerve-injured rats

Tolerance develops to the antiallodynic effects of the peripherally acting opioid loperamide hydrochloride in nerve-injured rats

Differential noxious and motor tolerance of chronic delta opioid receptor agonists in rodents

Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin

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