Effects of selective opiate antagonists on morphine-induced hyperalgesia in domestic fowl

Sufka, Kenneth J.; Hughes, Richard A.; Giordano, James

doi:10.1016/0091-3057(91)90588-s

Cited by 24 publications

(5 citation statements)

References 51 publications

(55 reference statements)

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“…This is consistent with clinical observations that OIH is an increase in nociceptive sensations whereas other senses are unchanged [32; 88]. Opiate receptors, especially the mu-opiate receptor (MOR), are critically involved in OIH [17; 66; 86] and MOR-deficient mice are not hyperalgesic after opiate treatment [46]. We suggest that MORs on small diameter DRG neurons are instrumental in initiating OIH.…”

Section: Discussionsupporting

confidence: 86%

GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats

Gong

Bhargava

Jasmin

2016

Pain

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The contribution of the peripheral nervous system to opiate-induced hyperalgesia (OIH) is not well understood. Here, we determined the changes in excitability of primary sensory neurons after sustained morphine administration for 7 days. Changes in expression of glutamate receptors and glutamate transporters after morphine administration were ascertained in dorsal root ganglions (DRGs). Patch clamp recordings from intact DRGs (ex-vivo preparation) of morphine-treated rats showed increased excitability of small diameter (≤ 30 μm) neurons with respect to rheobase and membrane threshold, whereas the excitability of large diameter (> 30 μm) neurons remained unchanged. Small diameter neurons also displayed increased responses to glutamate, which were mediated mainly by GluN2B containing NMDA receptors (NMDARs), and to a lesser degree by the neuronal excitatory amino acid transporter 3 /excitatory amino acid carrier 1 (EAAT3/EAAC1). Co-administration in vivo of the GluN2B selective antagonist Ro 25-6981 with morphine for 7 days prevented the appearance of OIH and increased morphine-induced analgesia. Administration of morphine for 7 days led to an increased expression of GluN2B and EAAT3/EAAC1, but not of the AMPA, kainate or Group I metabotropic glutamate receptors, or of the vesicular glutamate transporter 2 (VGLUT2). These results suggest that peripheral glutamatergic neurotransmission contributes to OIH and that GluN2B subunit of NMDARs in the periphery may be a target for therapy.

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Section: Discussionsupporting

confidence: 86%

GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats

Gong

Bhargava

Jasmin

2016

Pain

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“…Similarly, Tilson et al [ 4 ] first demonstrated that abrupt cessation of opioids induced decreased pain thresholds in rats and showed that this enhanced pain sensitivity was highly correlated with the administered dose of opioid. Other animal studies followed, [ 2 , 5 , 6 , 7 ] all supporting the occurrence of OIH. Consistent with these animal results, clinical investigators demonstrated the occurrence of OIH after intraoperative remifentanil infusion, characterized by increased pain, combined with increased consumption of postoperative opioid, which in turn, resulted in decreased opioid efficacy [ 8 ].…”

Section: Evidencementioning

confidence: 84%

Opioid induced hyperalgesia in anesthetic settings

Lee

Yeomans

2014

Korean J Anesthesiol

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Pain is difficult to investigate and difficult to treat, in part, because of problems in quantification and assessment. The use of opioids, combined with classic anesthetics to maintain hemodynamic stability by controlling responses to intraoperative painful events has gained significant popularity in the anesthetic field. However, several side effects profiles concerning perioperative use of opioid have been published. Over the past two decades, many concerns have arisen with respect to opioid-induced hyperalgesia (OIH), which is the paradoxical effect wherein opioid usage may decrease pain thresholds and increase atypical pain unrelated to the original, preexisting pain. This brief review focuses on the evidence, mechanisms, and modulatory and pharmacologic management of OIH in order to elaborate on the clinical implication of OIH.

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“…MOR could form a molecular complex with TRPM8 to enable the activation of PLD, similarly to other G protein-coupled receptors (GPCRs), 15, 32, 72 as was recently shown for 5HT1b and TRPM8. 89 MOR is critical to OIH 82 and presumed to be also key to morphine induced cold hyperalgesia. MOR and TRPM8 are mainly expressed in small sized DRG neurons.…”

Section: Discussionmentioning

confidence: 99%

Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia

Gong

Jasmin

2017

The Journal of Pain

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It is not uncommon for patients chronically treated with opioids to exhibit opioid induced hyperalgesia (OIH), and this has been widely reported both clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate (NMDA) receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in OIH. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels both by patch clamp recording on sensory neurons and western blot on dorsal root ganglia (DRGs). The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine treated rats. Also, TRPM8 knockout mice (KO) failed to develop cold hyperalgesia after chronic administration of morphine. Our results demonstrate that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. Perspective Patients receiving chronic opioid are sensitive to cold. We now show in mice and rats that sustained morphine administration induces cold hyperalgesia and an up-regulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine induced cold hyperalgesia suggesting TRPM8 is regulated by opioids.

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Effects of selective opiate antagonists on morphine-induced hyperalgesia in domestic fowl

Cited by 24 publications

References 51 publications

GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats

GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats

Opioid induced hyperalgesia in anesthetic settings

Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia

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