Persistent inflammatory nociception increases levels of dynorphin1-17 in the spinal cord, but not in supraspinal nuclei involved in pain modulation

Parra, Michelle C.; Nguyen, Tuyet N.; Hurley, Robert W.; Hammond, Donna L.

doi:10.1054/jpai.2002.125185

Cited by 18 publications

(19 citation statements)

References 53 publications

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“…Persistent peripheral inflammation increases expression and release of endogenous opioids (Millan et al, 1986, Iadarola et al, 1988, Noguchi et al, 1992, Cabot et al, 1997, Hurley and Hammond, 2000, Parra et al, 2002. It could therefore be thought that activation of MOR by endogenous opioids may be responsible for the enhanced density of membraneassociated DOR in lumbar spinal cord and DRG neurons (Gendron et al, 2006) in CFA animals and, by way of consequence, for the potentiation of deltorphin II's analgesic effect reported here.…”

Section: Discussionmentioning

confidence: 65%

“…Inflammation is known to induce the release of endogenous opioids (Millan et al, 1986, Iadarola et al, 1988, Noguchi et al, 1992, Cabot et al, 1997, Hurley and Hammond, 2000, Parra et al, 2002. To determine whether activation of MOR by an endogenous opioid during inflammation was involved in the regulation of DOR and deltorphin II-mediated analgesia, we tested antihyperalgesic effects of deltorphin II (2.5 μg, intrathecal) in pENK-, β-END-, pDYN-KO mice and littermate controls.…”

Section: Contribution Of Endogenous Opioids In Deltorphin Ii-induced mentioning

confidence: 99%

“…In the present study we tested the hypothesis that inflammationinduced release of endogenous opioids have been responsible for the increased cell surface expression of DOR following inflammation. Because KOR has been shown to interact with DOR (Jordan and Devi, 1999) and in particular because peripheral inflammation induces the release of dynorphin in various brain areas and in the spinal cord (Millan et al, 1986, Iadarola et al, 1988, Parra et al, 2002, a role for KOR in the regulation of DOR was also considered.…”

Section: Introductionmentioning

confidence: 99%

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Essential role of mu opioid receptor in the regulation of delta opioid receptor–mediated antihyperalgesia

2007

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Analgesic effects of delta opioid receptor (DOR)-selective agonists are enhanced during persistent inflammation and arthritis. Although the underlying mechanisms are still unknown, membrane density of DOR was shown to be increased 72 h after induction of inflammation, an effect abolished in mu opioid receptor (MOR)-knockout (KO) mice (Morinville et al., 2004b). In this study, we demonstrated a crucial role of MOR in DOR-mediated antihyperalgesia. Intrathecal administration of the DOR selective agonist deltorphin II failed to induce antihyperalgesic effects in MOR-KO mice, whereas it dose-dependently reversed thermal hyperalgesia in wildtype mice. The antihyperalgesic effects of deltorphin II were blocked by naltrindole but not CTOP suggesting that this agonist was mainly acting through DOR. SNC80-induced antihyperalgesic effects in MOR-KO mice were also attenuated as compared to littermate controls. In contrast, kappa opioid receptor knockout did not affect deltorphin II-induced antihyperalgesia. As evaluated using mice lacking endogenous opioid peptides, the regulation of DOR's effects was also independent of β-endorphin, enkephalins, or dynorphin opioids known to be released during persistent inflammation. We therefore conclude that DOR-mediated antihyperalgesia is dependent on MOR expression but that activation of MOR by endogenous opioids is probably not required.

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Section: Discussionmentioning

confidence: 65%

Section: Contribution Of Endogenous Opioids In Deltorphin Ii-induced mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Essential role of mu opioid receptor in the regulation of delta opioid receptor–mediated antihyperalgesia

2007

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“…Peripheral inflammation is known to increase the release of endogenous opioid peptides, both in the periphery (Cabot et al, 1997) and in the CNS (Millan et al, 1986(Millan et al, , 1988Iadarola et al, 1988;Hurley and Hammond, 2001;Parra et al, 2002). Specifically, unilateral inflammation of the hindlimb was reported to rapidly increase both the mRNA levels of dynorphin and enkephalin precursors (Iadarola et al, 1988;Noguchi et al, 1992) as well as the level of immunoreactive dynorphin (Iadarola et al, 1988;Millan et al, 1988;Parra et al, 2002). Bilateral changes in the level of met-and leu-enkephalin peptide content were also observed in the superficial dorsal horn of the rat spinal cord 5 weeks after CFA injection (Millan et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin

et al. 2007

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Abstract-We previously showed that prolonged morphine treatment and chronic inflammation both enhanced delta opioid receptor (␦OR) cell surface density in lumbar spinal cord neurons. Here, we sought to determine whether administration of morphine to rats with chronic inflammation would further increase the bio-availability of ␦OR, and thereby the analgesic properties of the ␦OR agonist deltorphin, over that produced by inflammation alone. We found that chronic inflammation produced by injection of complete Agonists acting through the mu opioid receptor ( OR), such as morphine and its derivatives, induce potent analgesic effects (Bodnar and Klein, 2004). However, they also give rise to undesirable side-effects such as nausea, constipation, and respiratory depression (Colpaert, 1996;Kreek, 1996). In addition, chronic stimulation of OR induces tolerance and physical dependence (Cowan et al., 1988). By contrast, drugs acting on ␦OR produce more limited analgesia, but also give rise to considerably less undesirable side-effects and induce virtually no tolerance (Porreca et al., 1984;May et al., 1989; Sheldon et al., 1990;Szeto et al., 1999;Gallantine and Meert, 2005). For these reasons, ␦OR agonists have been proposed as possible alternatives to OR agonists for the treatment of chronic pain, including neuropathic (Mika et al., 2001;Petrillo et al., 2003;Morinville et al., 2004a) and chronic inflammatory pain (Desmeules et al., 1993;Stewart and Hammond, 1994;Fraser et al., 2000;Hurley and Hammond, 2000;Qiu et al., 2000;Cahill et al., 2003;Petrillo et al., 2003).One of the reasons for the relatively poor analgesic efficiency of ␦OR agonists may be that only a small proportion of ␦OR is actually present on neuronal plasma membranes under baseline conditions (Cheng et al., 1995(Cheng et al., , 1997Elde et al., 1995;Zhang et al., 1998;Cahill et al., 2001a). However, under conditions of chronic inflammation, such as produced in rodents by injection of complete Freund's adjuvant (CFA) in the hind paw, we observed a massive recruitment of ␦OR from intracellular stores to the plasma membrane in neurons of the dorsal horn of the spinal cord Morinville et al., 2004b). This increase in the pharmacological availability of ␦OR was postulated to account for the enhanced antihyperalgesic efficacy of the centrally administered ␦OR agonists reported in conditions of chronic inflammation (Hylden et al., 1991;Stewart and Hammond, 1994;Fraser et al., 1 Present address: Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4. *Corresponding author. Tel: ϩ1-514-398-1913; fax: ϩ1-514-398-5871. E-mail address: alain.beaudet@mcgill.ca (A. Beaudet). Abbreviations: CFA, complete Freund's adjuvant; DRG, dorsal root ganglion; Fluo-DLT, -Bodipy 576/589 deltorphin-I 5-aminopentylamide; i.t., intrathecal/intrathecally; MPAHE, maximum possible antihyperalgesic effect; MPE, maximum possible antinociceptive effect; MS, morphine sulfate; OR, mu opioid receptor; PB, phosphate buffer; RI...

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“…First, a number of studies in male rats have reported that the antihyperalgesic properties of opiates change in the presence of persistent inflammation, becoming more potent over time (26,33,54). Several mechanisms have been implicated, including changes in peripheral (55), spinal (18,49,50), and supraspinal (26,27) opioidergic circuits. Second, persistent pain influences the ovulatory cycle and, therefore, the hormonal status of females.…”

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confidence: 99%

Persistent pain model reveals sex difference in morphine potency

Wang¹,

Traub²,

Murphy³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Persistent inflammatory nociception increases levels of dynorphin1-17 in the spinal cord, but not in supraspinal nuclei involved in pain modulation

Cited by 18 publications

References 53 publications

Essential role of mu opioid receptor in the regulation of delta opioid receptor–mediated antihyperalgesia

Essential role of mu opioid receptor in the regulation of delta opioid receptor–mediated antihyperalgesia

Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin

Persistent pain model reveals sex difference in morphine potency

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