A Single Dose of Intrathecal Morphine in Rats Induces Long-Lasting Hyperalgesia: The Protective Effect of Prior Administration of Ketamine

Elstraete, Alain C. Van; Sitbon, Philippe; Trabold, Fabien; Mazoit, Jean‐Xavier; Benhamou, Dan

doi:10.1213/01.ane.0000184136.08194.9b

Cited by 63 publications

(43 citation statements)

References 41 publications

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“…This paradoxical effect has been demonstrated both in clinical (Guignard et al, 2000;Angst et al, 2003;Compton et al, 2003) and laboratory studies (Laulin et al, 1998;Celerier et al, 1999Celerier et al, , 2000Celerier et al, , 2001Laulin et al, 2002;Van Elstraete et al, 2005). Morphine, at higher doses, induces analgesia.…”

Section: Introductionmentioning

confidence: 91%

Signaling pathway of morphine induced acute thermal hyperalgesia in mice

Galeotti

Stefano

Guarna

et al. 2006

Pain

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Systemic administration of morphine induced a hyperalgesic response in the hot plate test, at an extremely low dose (1-10 lg/kg). We have examined in vivo whether morphine, at an extremely low dose, induces acute central hypernociception following activation of the opioid receptor-mediated PLC/PKC inositol-lipid signaling pathway. The PLC inhibitor U73122 and the PKC blocker, calphostin C, dose dependently prevented the thermal hypernociception induced by morphine. This effect was also prevented by pretreatment with aODN against PLCb 3 at 2 nmol/mouse and PKCc at 2-3 nmol/mouse. Low dose morphine hyperalgesia was dose dependently reversed by selective NMDA antagonist MK801 and ketamine. This study demonstrates the presence of a nociceptive PLCb 3 /PKCc/NMDA pathway stimulated by low concentrations of morphine, through lOR 1 receptor, in mouse brain. This signaling pathway appears to play an opposing role in morphine analgesia. When mice were treated with a morphine analgesic dose (7 mg/kg), the downregulation of PLCb 3 or PKCc at the same aODN doses used for the prevention of the hyperalgesic effect induced, respectively, a 46% and 67% potentiation in analgesic response. Experimental and clinical studies suggest that opioid may activate pronociceptive systems, leading to pain hypersensitivity and short-term tolerance, a phenomenon encountered in postoperative pain management by acute opioid administration. The clinical management of pain by morphine may be revisited in light of the identification of the signaling molecules of the hyperalgesic pathway. Ó

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Section: Introductionmentioning

confidence: 91%

Signaling pathway of morphine induced acute thermal hyperalgesia in mice

Galeotti

Stefano

Guarna

et al. 2006

Pain

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“…The aim of this study was to evaluate the ability of the NMDA-receptor antagonist, DEX, to diminish OIH to experimental pain in a wellcharacterized sample of MM individuals. Given the ability of the potent NMDA antagonists, ketamine (Celerier et al 2000;Duncan & Spiller 2002;Angst et al 2003;Mercadante, Villari & Ferrera 2003b;Anghelescu & Oakes 2005;Holtman & Wala 2005;Van Elstraete et al 2005) and MK801 (in animals) Li et al 2001), to counteract OIH and opioid tolerance, the well-tolerated, but weaker, DEX was chosen for evaluation. It was hypothesized that DEX therapy would effectively increase tolerance for experimental pain in this sample, and thus suggest an excitatory amino acid mechanism underlying their notable hyperalgesia.…”

Section: Introductionmentioning

confidence: 99%

CLINICAL STUDY: Lack of effect of chronic dextromethorphan on experimental pain tolerance in methadone‐maintained patients

Compton¹,

Ling

Torrington

2008

Addiction Biology

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Good evidence exists to suggest that individuals on opioid maintenance for the treatment of addiction (i.e. methadone) are less tolerant of experimental pain than are matched controls or exopioid addicts, a phenomenon theorized to reflect opioid-induced hyperalgesia (OIH). Agonist activity at the excitatory ionotropic N-methyl-D-aspartate (NMDA) receptor on dorsal horn neurons has been implicated in the development of both OIH and its putative expression at the clinical level-opioid tolerance. The aim of this study was to evaluate the potential utility of the NMDA-receptor antagonist, dextromethorphan (DEX), to reverse or treat OIH in methadonemaintenance (MM) patients. Utilizing a clinical trial design and double-blind conditions, changes in pain threshold and tolerance [cold pressor (CP) and electrical stimulation (ES)] following a 5-week trial of DEX (titrated to 480 mg/day) in comparison with placebo was evaluated in a wellcharacterized sample of MM patients. The sample (n = 40) was 53% male and ethnically diverse (53% Latino, 28% African American, 10% White, 9% other), with a mean age of 48.0 years (SD = 6.97). Based on t-test analyses, no difference was found between groups on CP pain threshold, CP pain tolerance, ES pain threshold or ES pain tolerance, both pre-and postmedication. Notably, DEX-related changes significantly differed by gender, with women tending to show diminished tolerance for pain with DEX therapy. These results support that chronic high-dose NMDA antagonism does not improve tolerance for pain in MM patients, although a gender effect on DEX response is suggested.

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“…enhanced pain response to noxious stimuli). Opioid-induced hyperalgesia has been demonstrated in many animal studies (1,(5)(6)(7)(8), and even brief exposure to fentanyl or morphine can induce long-lasting hyperalgesia (8,9). Hyperalgesia also occurs in patients after administration of various opioids (10 -12).…”

mentioning

confidence: 99%

Chronic Opioid Potentiates Presynaptic but Impairs Postsynaptic N-Methyl-d-aspartic Acid Receptor Activity in Spinal Cords

Zhao

Chen

et al. 2012

Journal of Biological Chemistry

116

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Background:We determined the role of presynaptic N-methyl-D-aspartate receptor (NMDAR) activity in spinal cords in opioid-induced hyperalgesia and tolerance. Results: Chronic opioid increases presynaptic NMDAR activity at primary sensory nerve terminals through protein kinase C. Conclusion: Increased presynaptic NMDAR activity potentiates nociceptive input and is responsible for opioid hyperalgesia and tolerance. Significance: Understanding mechanisms of increased NMDAR activity is important for improving opioid therapies.

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A Single Dose of Intrathecal Morphine in Rats Induces Long-Lasting Hyperalgesia: The Protective Effect of Prior Administration of Ketamine

Cited by 63 publications

References 41 publications

Signaling pathway of morphine induced acute thermal hyperalgesia in mice

Signaling pathway of morphine induced acute thermal hyperalgesia in mice

CLINICAL STUDY: Lack of effect of chronic dextromethorphan on experimental pain tolerance in methadone‐maintained patients

Chronic Opioid Potentiates Presynaptic but Impairs Postsynaptic N-Methyl-d-aspartic Acid Receptor Activity in Spinal Cords

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